{"paper_id":"4ae66936-1bb4-4a56-bcad-0dc02cd70715","body_text":"International Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 1 \n \nA Brief Overview on Female Infertility, It's \nCauses and Diagnostic Approaches \nKrishna Takankhar1, Diksha Gupta2, Rajesh Oswal3 \n1Research Student,  Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune, India. \n2Assistant Professor, Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune, India. \n3Principal, Genba Sopanrao Moze College of Pharmacy, Wagholi, Pune, India. \n \nABSTRACT \nFemale infertility is the major disorder which has altered the man kind foe lack of conception  and \nreproducibility, stressful world, excess radiation, lack of biological food, genetically  disorder ,changing \nlife style, increased electronic discharge have resulted the female infertility. Infertility/ childlessness \ncause great personal suffering & distress. Most of this  agony & misery is hidden from the public gaze. \nThat is the reason this topic is not discussed  about openly. The dismal ignorance & neglect about the \ncauses of childlessness and its  treatment are main reason for the lack of public support for childless \ncouple. Female fertility can be limited or diminished or destroyed in a number of ways. Women have a \nfinite number  of germs cells and follicles that are available for a limited period, from menarche to \nmenopause, during their lifetimes. The process of ovulation is mediated by the interactions of  \nhypothalamic, pituitary and ovarian hormones. Interference with ovulation can occur at any  one or \ncombinations of these sites. The oviducts can be distorted or blocked by the consequences of \nendometriosis or infection. The quality of the ova and spontaneous pregnancy decreases steadily with \nage. Drugs are available that stimulate ovulation and donor  eggs can be used. The cryopreservation of \nova or ovarian tissue is technique now receiving  research attention. Diagnosis is straightforward when \ncauses are severe and laparoscopy is  still the preferred method for assessing for tubal factor infertility \nand endometriosis. IVF remains the dominant treatment, although traditional measures still have a major \nrole. Internationally, IVF opportunities are limited in view of cost. About 10 -15% of couples experience \nsome difficulty with fertility. Remedies range from a visit to a primary physician,  education and \nadjustments in timing attempts to conceive, to placing the entire reproductive  process in the hands of \nspecialist.The purpose of the study is to evaluate existing literature for  possible associations between \nfemale infertility, infertility-associated diagnoses, and the following areas of disease: infertility and \nmental health significance of the study common  factors ,diagnosis methods artificial fertility treatment \nmethods ethical issues about \n \nKeywords- Infertility, IVF, ART, Endoscopy, Miscarriage \n \nINTRODUCTION \nInfertility is a medical condition that can cause psychological, physical, mental, spiritual, and  medical \ndetriments to the patient. The unique quality of this medical condition involves affecting both the patient \nand the patient's partner as a couple. Although male infertility is an  important part of any infertility \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 2 \n \ndiscussion, this paper will review the evaluation, management,  and treatment of female infertility. One \nmust understand normal fecundability, the probability of achieving pregnancy in one menstrual cycle, to \nunderstand infertility. This basic understanding will help the healthcare team properly counsel the \npatient on referrals and provide basic education and understanding of this medical condition. \nThe research community has established a fecundability rate multiple times, which has helped establish \nnormal pregnancy rates to assist in diagnosing infertility. The largest study  identified that 85% of \nwomen would conceive within 12 months. Based on this study's  findings, fecund a bility is 25% in the \nfirst three months of unprotected intercourse and then  decreased to 15% for the remaining nine \nmonths.[1]This research has helped the American  Society of Reproductive Medicine (ASRM) establish \nwhen a couple should undergo an infertility evaluation. The ASRM recommends initiating an evaluation \nfor infertility after  failing to  achieve pregnancy within 12 months of  unprotected intercourse or \ntherapeutic donor insemination in women younger than 35 years or within 6 months in women older \nthan 35.[2] \n \nINFERTILITY AND MENTAL HEALTH \nSix studies included in this review  evaluated the impact  of infertility on mental health.  Universally, \nauthors concluded that women with  a history of  infertility or  an infertility- related diagnosis, \nspecifically PCOS, were at increased risk to develop mental health disorders [3]. Four out of the six \nstudies that found correlations with mental health issues used  women with PCOS as their primary \npopulation [4] Depression risk was found to be elevated in  four out of the six studies based on scores \nfrom validated scales such as the Edinburgh  Depression Scale [5]. Five of the six studies noted \nsignificant increases in diagnoses of anxiety or psychosocial distress in the specific study populations [6] \nThe sole study which did not find an increase in anxiety was by Baldur -Felskov et al. This  study was a \nretrospective cohort study published in 2013 that included 98,320 Danish women  who were evaluated \nfor infertility between 1973 and 2008, with a median follow up of \n11.3 years. Women who sought infertility treatment were tracked through medical registries to \ndetermine rates of subsequent psychiatric hospitalizations. While there was no statistically  significant \nincrease in hospitalizations related to anxiety in the PCOS/infertile population, it is difficult to assess \nwhether actual levels of anxiety were elevated but simply did not lead to  subsequent hospitalizations. A \nmain drawback of the Baldur -Felskov study was the fact that  only inpatient hospitalizations were \ntracked, likely underestimating the true correlation between infertility and psychiatric disease. \nImportantly, the Baldur -Felskov study did note a  significant increase in hospitalizations related to \nalcohol and drug abuse in the PCOS/infertile population [7] \n \nEPIDIMIOLOGY \nInfertility is a complex disorder with significant medical, psychosocial, and economic problems [8]. \nData from population - based studies suggest that 10 -15 % of couples in the  world experience infertility \n[9]. In Africa, its prevalence i s particularly high in sub -Sahara ranging from 20% to 60% of couples \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 3 \n \n[10]. It is estimated that female factors and unexplained  infertility accounts for 50 -80% while the male \nfactor accounts for 20 -50% of the cause of  infertility in different parts of Nigeria [11]. Available \nevidence suggests that the social consequences of infertility are particularly profound for African \nwomen as compared to  men[12]. Community based data suggest that up to 30 per cent of couples in \nsome parts of Nigeria may have proven difficulties in achieving a desired conception after two years of  \nmarriage without the use of contraceptives [13] \nSIGNIFICANCE OF THE STUDY \nInfertile women should seek counseling and consider natural at home options for feelings of  sadness, \nand depression. Not doing anything about it and keeping it to her isn't going to help.  Cruel feelings of \nloss, depression and trauma are so stressful emotionally and psychologically  that they can lead to \nphysical manifestations in the body; actually affect physical functions of the body. Once psychological \nhealth affects the physical body, the situation gets worse than  physical symptoms feed the \ndepression.[14] Infertility is a very real part of millions of people's  lives, and all of those going through \nthese deserve to be heard and guided to psychological  health support on this cruel  journey. In fact, the \npsychological health aspect of  infertility needs to be part of every couple's health plan. Whether a \ncouple decides to continue to pursue  parenthood or not, a psych ological health plan must be part of the \noverall picture.[15] Akker (2005) mentioned that, investigations on infertility are voluminous and have \nshown that  involuntary childlessness can be devastating, and it is associated with psychological \ndistress.[16] Infertility seem to have comprehensive effects in woman's life, it is not only restricted to \nsexual or reproductive areas of life but also impact  burden on several  psychosocial areas of  human \nexistence.[16,17,18,19] Impairments have been reported regarding  distinct aspects, such as relationship \nabilities, psychopathology,  family life, marital life, and economic terms. [20 21 22] Beauty of life for \nchildren and we do not  have a happy life without them. Deprivation from the  grace of reproduction is \nmeaningless life and the couple's relationship getting in the deterioration and lacks stability. If \ninfertility period is prolonged, it put a childless woman in severe pressure on herself, may  become \ndepressed and concern for her married life, and sometimes because they have lost the most important role \nof her creation, moreover her marriage became threatens. These increase  Psychological disorders and \ndepression symptoms, especially if the husband isn't a concerted. \n \nOPERATIONAL DEFINATIONS \n \nInfertility: Infertility, as defined by the World Health Organization, is a disease of the  reproductive \nsystem defined by the failure to achieve a clinical pregnancy after 12 months or more of regular \nunprotected sexual intercourse, without the use of contraception.[23] \nPrimary infertility: Couples who have been no prior conception after at least one year,  having sex \nwithout usage birth control methods.[24] \nSecondary infertility: Couples who have been able to get pregnant at least once, but now are  unable to \nconceive.[24] \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 4 \n \nPsychological distress: A state of emotional suffering that may impact on social functioning  and day to \nday living of individuals characterized by symptoms of depression, anxiety, stress and tension.[25, 26] \n \nTHE MOST COMMON IDENTIFIABLE FACTORS OF FEMALE INFERTILITY \n \n Ovulatory disorders - 25% \n Hyperprolactinemia-7% \n Pelvic adhesions-12% \n Tubal blockage-11% \n Other tubal/congenital uterian anomalies-11% \n Endometriosis-15% \nFig no.1:- Tests for ovulation function. \nEach of these causes will be further investigated in later portions of this paper. Male and  unknown \nfactors are outside the scope of this paper and will be discussed elsewhere. Even though these factors are \nnot discussed here, it is important to realize that male factor infertility represents a substantial portion of \nthe identifiable factors causing infertility. \n \nANOVULATION \nDisorders of anovulation account for about 30% of infertility and often present with irregular  periods \n(oligomenorrhoea) or an absence of periods (amenorrhoea). Many of the treatments  are simple and \neffective, so couples may need only limited contact with doctors. This makes it easier for a couple to \nmaintain a private loving relationship than in the stressful, more  technological environment of assisted \nconception. However, not all causes of anovulation are  amenable to treatment by ovulation induction. \nAnovulation can sometimes be treated with  medical or surgical induction, but it is the cause of the \nanovulation that will determine whether ovulation induction is possible[27] \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 5 \n \nHYPOTHALAMIC-PITUITARY CAUSES:- \nHypogonadotropic hypogonadism is characterized by a selective failure of the pituitary gland to produce \nFSH and LH. The commonest cause is excessive exercise, being underweight, or  both. Women who \nhave a low body mass index (BMI), f or example <18Kg/m2 or who  exercise excessively, for example \ngymnasts, marathon runners, ballerinas, may develop amenorrhoea because of a physiological reduction \nin the hypothalamic production of gonadotropin releasing hormone. Women who are underweight for \ntheir height when they get  pregnant are more likely to have .small for dates. babies; and children of \nwomen who have  eating disorders are more likely to be admitted to hospital with failure to thrive. \nSheehan.s syndrome (panhypopituitarism), caused by infarction of the anterior pituitary venous complex \n(usually after massive postpartum haemorrhage or trauma), and Kallman.s syndrome (amenorrhoea with \nanosmia caused by congenital lack of hypothalamic production of gonadotropin releasing hormone) are \nrare. Children treated for a craniopharyngioma or some forms of leukaemia may have hypogonadotropic \nhypogonadism secondary to cerebral irradiation, which may affect the hypothalamus or the pituitary[27] \nOVARIAN CAUSES:- \nPolycystic ovary syndrome is the commonest cause (70%) of anovulatory infertility [28-32] The primary \nabnormality seems to be an excess of androgen production within the ovary[33,34] that  leads to the \nrecruitment of large numbers of small preovulatory follicles, which fail to respond to normal \nconcentrations of follicle stimulating hormone[35]. Thus, a dominant follicle is rarely produced. \nWomen with polycystic ovary syndrome commonly present their  late teens or early 20s with hirsutism, \nacne, or irregular periods (cycle length > 35days).  Even if they ovulate, the chance of conception for \nthese women is reduced because fewer ovulatory  events occur in a given time frame. Obesity is present \nin varying degrees (30% to 70%) in women with the syndrome and is usually of the central type [36-38]. \nCentral obesity, being a  prominent feature of the so-called metabolic syndrome, is directly linked to \nincreased peripheral insulin resistance (IR) [39]. Furthermore, PCOS itself has been shown to confer a  \nrisk for insulin resistance, beyond that caused by obesity alone[40] \n \nfig no.2:-normal ovary and polycystic ovary \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 6 \n \nCAUSES UNSUITABLE FOR OVULATION INDUCTION \nPremature ovarian failure:-Premature ovarian failure (POF) is the cessation of ovarian  function before \n40 years of age. The term  refers to the condition when the ovaries have lost  their germinative and \nhormonal functions because of the exhaustion of the number of ovarian  follicles prior to the typical age \nfor physiological menopause, which in Poland averages 51 years [41]. \nThe physician may encounter this condition when examining a young female patient who is  struggling \nto get pregnant or is experiencing secondary amenorrhoea. In order to make a  diagnosis in the case of a \nyoung female, it might be helpful to determine if there a re any menopausal symptoms. The medical \nhistory of patients with POF usually reveals a normal age of menarche [42 43] and regular menstrual \ncycles, followed by oligomenorrhoea or sudden  amenorrhoea. In some cases, secondary loss of menses \nis diagnosed after stopping contraceptive pills [44-46]. Most frequently, women suffer from hot flushes, \nexcessive sweating, hair loss, as well as skin and mucous membrane dryness \nGenetic abnormality -The commonest genetic abnormality is Turner.s syndromeTurner  syndrome was \nfirst reported as a clinical syndrome (prior to the availability of karyotyping) in seven women with short \nstature, sexual immaturity, neck webbing, and cubitus valgus in a  paper published in 1938 by Henri \nTurner, an Oklahoma physician [47]. However,  Otto Ulrich had already described an eight-year-old girl \nwith a similar phenotype several years earlier [48]. \nTurner syndrome is the most common sex chromosome abnormality in females and occurs in  \napproximately 1 in 2000 to 1 in 2500 live female births, based on epidemiological and newborn genetic \nscreening data from Europe, Japan, and the United States [49 -51]. The true  prevalence of Turner \nsyndrome remains difficult to ascertain because patients with a milder phenotype may remain \nundiagnosed. Some indiv iduals are not diagnosed until late adulthood  if their phenotype is mild [52]. \nTurner syndrome occurs with more or less the same prevalence in all ethnic groups and in  different \ncountries. However, the prevalence  at birth may be  declining in some countries. This is related to the \nincreased use of ultrasonographic screening prenatally and the fact that  some mothers carrying fetuses \nwith Turner syndrome choose to terminate the pregnancy [53 54] . On the other hand, most gestations \n(likely more than 99 percent) affected by X chromosome monosomy (45,X) do not survive to birth. The \n45,X genotype is found in at least 10 percent of all spontaneous abortions [55-59]The diagnosis of TS \ncould be obtained prior to birth using  prenatal diagnostic testing such as  chorionic villus sampling or \namniocentesis. Using those tests, an analysisof the fetal chromosomal structure would defiantly confirm \nthe diagnosis. TS  should be clinically suspected in thepresence of prodromal symptoms. For example, \nthepresence of fetal hydrops, cystic hygroma, or cardiac defects on  a prenatal ultrasound would raise \nthe suspicionof TS [60 61]. Post-delivery karyotype testing is often required to  confirmthe diagnosis. In \ncases where the TS is a result ofmosaicism, karyotype can come back normal. If a high suspicion of TS \nremains despite a normal  karyotype,fluorescence in situ hybridization analysis can offer an additional \nmodality to the karyotype [60].Later in life, patients with TS who went undiscovered might present with \ndevelopmental abnormalities such asthe delayed onset of puberty or amenorrhea. A high concentration \nof the follicle - stimulating hormone is highlyindicative of TS. Anti-Mullerian hormone offers a \nhighlysensitive marker for ovarian failure prediction [62 63]. \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 7 \n \nOVULATION INDUCTION \nTreating specific causes \nWaight change -Weight reduction through dietary modification and exercise is recommended  for \noverweight PCOS patient [64]. Some studies show that over 10% of women with PCOS will regain \nspontaneous ovulation when placed on  low calorie, low -fat diet, and exercise or  with surgery. The aim \nof dietary  restriction and  exercise is toward  losing about 5 –10% of  their body weight. This form of \ntreatment alone or in combination with pharmacologic agents  would reduce insulin resistance and is \nadvocated for overweight to obese women of BMI > 24 [64]. The drawbacks of this method of \ntreatment are that such women lack the motivation to remain on diet and exercise, and may not be able to \nachieve the desired weight loss to trigger  spontaneous ovulation, and most times pharmacologic agents \nare added to assist ovulation.  The duration it takes to achieve the desired body weight to bring about \novulation is not  defined, but differs among patients. Other drawbacks are that it may not trea t \nanovulation in  normal-weight women even though they also have insulin resistance as well. The \nadvantage is that it is cost -effective and will not produce any form of drug reactions. It will also reduce  \nthe high level of luteinizing hormone and reduce early pregnancy loss. A combination of  lifestyle \nmodification with weight loss before pharmacologic ovulation-inducing agents improved ovulation and \nlive birth in women with PCOS in a USA study [65] and in addition,  required lower doses of  \npharmacologic agent for ovulation induction. \n \nHYPERPROLACTINEMIA \nThe prevalence of hyperprolactinemia ranges from 0.4% in unselected normal adult females to as high \nas 9%–17% in 1,2 females with reproductive health disorders. Its prevalence was  found to be 5% in a \nfamily planning clinic, 9% in women with adult -onset amenorrhea, and  17% among women  with 1 \npolycystic ovary syndrome.[66] \nDiagnostic evaluation -For the correct identification of the etiology of hyperprolactinemia,  some \nparameters must be taken into accoun t: medical history, physical examination, clinical  features, \nlaboratory findings (especially PRL serum levels), as well as imaging studies of the  pituitary and sella \nturcica. Furthermore, the screening for macroprolactinemia should often be considered. \nIn addition to PRL determination, TSH, free T 4 , and creatinine levels should be obtained to  rule out \nsecondary causes of hyperprolactinemia[67 68 69]. Moreover, acromegaly must be  investigated by \nmeans of IGF -1 measurement in all patients with a macroade nomas, even  though there are no \nmanifestations of this disease[70]. Finally, b-hCG measurement is mandatory in any childbearing \nwoman with amenorrhea[67 68] \nHypothyroidism-WHO estimates the overall prevalence of primary infertility in India to  be 3.5 - \n16.8%.2 Both hyperthyroidism and hypothyroidism have profound effects on estrogen  and androgen \nmetabolism, menstrual function and fertility [71] They may cause delayed onset  of puberty, menstrual \nabnormalities, anovulatory cycles, miscarriages and infertility.[72]Hypothyroidism can be easily \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 8 \n \ndetected by assessing serum thyroid stimulating  hormone (TSH) levels. A slight increase in TSH levels \nwith normal T3 and T4 indicates subclinical \nhypothyroidism whereas high TSH levels accompanied by low T3 and T4 levels in dicate clinical \nhypothyroidism. Elevated thyrotropin- releasing hormone levels due to hypothyroidism are often \nassociated with increased prolactin (PRL) levels and a delayed LH  response to GnRH. [73] Thyroid \ndysfunction is implicated in abroad spectrum of r eproductive disorders, ranging from abnormal sexual \ndevelopment to menstrual irregularities and infertility.[74] It has been proved that for normal sexual \nfunction, thyroid secretion of T3, T4  need to be approximately normal. We had conducted this study to  \ncollect some specific  information regarding hypothyroidism in infertile women and to assess their \nresponses in  treatment procedures. Diagnostic evaluation -Thyroid d ysfunction is a common cause of \ninfertility which can be easily managed by correcting the appropriate levels of thyroid hormones.[75 76] \nIt has been recommended that in the presence of raised TSH along with raised PRL levels, the treatment  \nshould be first to correct the hypothyroidism before evaluating further causes of hyperprolactinemia. \nHormone therapy with thyroxine is the choice of treatment in established  hypothyroidism. It normalizes \nthe menstrual cycle, PRL levels and improves the fertility rate.  Therefore, with simple oral treatment for \nhypothyroidism, 76.6% infertile women with hypothyroidism conceived after 6 weeks to 1 year of \ntherapy. We tried to maintain normal  TSH levels; compliance and adequacy of hypothyroid drug dose \nwere checked by TSH measurement after 6 to 8 weeks interval. \nTherefore, the normal TSH levels are the pre -requisite requirements for fertilization. The  decision to \ninitiate thyroid replacement therapy  in subclinical hypothyroidism at  early stage is justified in infertile \nwomen. Our data also indicate that variations in TSH levels in the  narrower range or borde rline cases, \ni.e. 4 –5, 5 –6, and >6.0 μIU/ml, should not be ignored in  infertile women which are otherwise \nasymptomatic for clinical hypothyroidism. This group of infertile women, if only carefully diagnosed \nand treated for hypothyroidism, can benefit a  lot rather than going for unnecessary battery of hormone \nassays and costly invasive procedures. For better management of infertility cause, we should plan \nfurther studies with the large sample size and long -term follow-up which are necessary to validate the \nvariation in TSH and PRL levels. \n \nPELVIC ADHESION \n \nIn the case of pelvic inflammatory disease, or any other infection of the reproductive tract, the \nfallopian tubes can become inflamed. The inflamed surfaces can develop scar tissue or  adhesions within \nthe tubes. These adhesions prevent egg and sperm from coming together.[77]Adhesions caused by \nendometriosis usually occur in the pelvic cavity. They may  be present near the fallopian tubes or \novaries. Endometrial adhesions may interfere with  ovulation.[78]Sometimes, endometrial adhesions \nprevent the fallopian tube from moving naturally. The ovary is not attached directly to the fallopian \ntubes. During ovulation, when an  egg is released from the ovary, it must find its way into the fallopian \ntube If adhesions interfere with the fallopian tubes natural movement, an egg may not make it into the \nfallopian tube.[79] This decreases fertility. \n \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 9 \n \nDiagnosis-If the adhesions are within the fallopian tubes, surgical repair may be \npossible.[80]However,IVF treatment may be more successful and cost-effective.If Asherman‟s \nsyndrome is the cause of infertility, the adhesions may be removed during an  operative hysteroscopy. \nYou may be able to conceive naturally afterward, or you may require  fertility treatment in addition to \nsurgery.[81]In the case of pelvic adhesions or endometriosis,  removal of the adhesions may reduce pain \nand may improve the odds of pregnancy success.  However, depending on the situation, you may still \nneed IVF or fertility treatment after surgery.[82] \n \nTUBAL BLOCKAGE-Blocked fallopian tubes are a common cause of infertility. Sperm  and an egg \nmeet in the fallopian tube for fertilization. A blocked tube can prevent them from  joining.If both tubes \nare fully blocked, pregnancy without treatment will be impossib le. If the  fallopian tubes are partially \nblocked, you can potentially get pregnant. However, the risk of an ectopic pregnancy increases.This is \nbecause it‟s harder for a fertilized egg to move through a blockage to the uterus. In these cases, your \ndoctor might recommend in vitro fertilization (IVF), depending on whether treatment is possible.If only \none fallopian tube is  blocked, the blockage most likely won‟t affect fertility because an egg can still \ntravel through the unaffected fallopian tube. Fertility drugs can help increase your chance of ovulating \non the open side \n \nHYSTEROSALPINGOGRAPHY (HSG): \nThe diagnosis of tubal patency based on radiologica lfindings is not considered a complete or  an \nabsolute diagnosis. X-ray gives an idea about the size and shapeof the uterine cavity, the isthmus and the \ncervical canalwhen viewing anteroposterior or profile films. [83] HSG iswidely  used and has some \nadvantages, including thelack of need for anesthesia, relative speed with which the procedure is \ncompleted, and a potential therapeutic effect with oil soluble contrast  media.[84] The therapeutic impact \nof HSG is, in part, due to the flushing of tubal debris. In addition, in-vitro studies have shown that oil-\nbased flushing media prevents peritoneal mast cell phagocytosis of spermatozoa and increases fecundity \nin subfertile mice. A pathognomonic finding on HSG is seen with SIN, in which the contrast  filled \ndiverticular projections result in a radiographically honeycombed appearance.[85]Hydrosalpinx also has \na characteristic appearance; however, transvaginal ultrasound better evaluates the volume of the dilated \ntubes.[86] HSG findings can be used to stage tubal  disease and the appearance of the intraluminal \nmucosal architecture as a  rugal  pattern  is a good prognostic  factor  forsubsequent pregnancy.[87 \n88] A potential limitation of HSG is tubal  spasm,  especially  with  elevated  contrast  injection  \npressure.  Based  on hysteroscopic tubalcannulation, it has been estimated that HSG may give a false \npositive diagnosis of proximal tubal obstruction 50 %  of the time. [ 8 9 ] Lower pressure, the use  \nof spasmolytic agents, such as glucagon, diazepam and terbutaline and follow -up imaging to  assess \ncontrast spillage following resolution of spasm have been proposed. [ 9 0 , 9 1 , 9 2 ] . However,  \nintermittent  tubalobstruction during HSG may suggest underlying tubal pathology, especially in the \nsetting of low injection pressures, and thus the value of spasmolytic agents may be limited.[90] \nFurthermore, the efficacy of these agents with respect to reversal of tubal spasm remainsto be \nestablished.[93 94]  A recent study suggested  thatunilateral cornual obstruction may be resolved in \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 10 \n \nmorethan 50% of patients by rotating the patient so that theobstructed tube is in a more inferior \nposition.[95] \nFig no.3:-hysterosalpingogram \n \nENDOSCOPIC EVALUATION \nWhen managing a woman with infertility, it is important to avoid missing the correct diagnosis and \ntreating a woman empirically for having an unexplained infertility, while existent tubal pathology might \nbenefit of surgery. HSG has been considered as a screening test for tubal pathology, making only \nabnormal results an indication for laparoscopy to confirm the diagnosis, exclude artifacts resulting from \ntransient tubal contractions and undergo a fertility -enhancing surgical intervention. However, many \nauthors have stressed on the relative low sensitivity and the false negative rates when using HSG alone. \nCompared to  laparoscopy, HSG has a sensitivity of 40 to 70% in the detection of bilateral tubal \nocclusion[96]Contrast intravasation into uterine and ovarian veins can be mistaken for tubal  filling, with \na false  negative rate reaching 50%  in proximal tubal occlusion, and 60% in distal tubal \nocclusion[97]Laparoscopy with direct visual examination of the pelvic anatomy is the  ideal method \navailable to diagnose tubal and peritoneal abnormalities that may impair fertility,  in contrast with HSG \nwhich can miss pelvic adhesions and endometriotic implants [98] When it  was first implemented, \nlaparoscopy was suggested as a mandatory step to rule out the existence of eendometriosis and peritubal \nadhesions as a cause of infertility, even when tubal  patency with free spillage of injected dye has been \ndemonstrated by HSG [99]great difference in the rate of abnormal findings was noted at that time \nbetween laparoscopy and the other  noninvasive tests. In 1975, the first published paper concluded that \nlaparoscopy frequently identifies a possible cause of infertility in women whose failu re to conceive has \nremained unexplained by other methods of investigation[100]The majority of these lesions are \nendometriotic ones, with accompanying tubal adhesions found in 20% of cases. Unilateral or  bilateral \ntubal occlusion could still be found as well in a minority of cases[96]Fallopian tubes can be patent under \nhigh pressures but dysfunctional physiologically [101]such abnormalities  can be corrected during \nlaparoscopy using neosalpingostomy, increasing therefore the pregnancy rates both spontaneously and \nwith IVF [102] \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 11 \n \nFig no 4:-laproscopy \n \nCONGENITAL UTERINE ANOMALIES \nCongenital uterine anomalies result from the abnormal differentiation, migration, fusion, and subsequent \ncanalization of Mullerian ducts during embryogenesis [103]. They have been  reported to be implicated \nas a potential cause of reduced fertility and miscarriages [104 -106]. Basing on anomalies in the \nembryological development process, the uterine malformations  can be divided in unification defects of  \nthe Mullerian du cts (unicornuate, bicornuate  or didelphys uterus), canalization defects for incomplete \nresorption of the midline septum (sub - septate or septate uterus), Mullerian agenesis and arcuate uterus \n[107]. Data from literature,  demonstrated that the aforementioned anomalies are present in 1-10% of \nunselected population, 2 -8% of infertile women and 5 -30% of women with a history of miscarriage \n[108]; however, the prevalence rate is uncertain due to the  application of several diagnostic methods \nsuch as hysterosalpingography, hysteroscopy, laparoscopy, magnetic resonance imaging and  three-\ndimensional sonography. In the same view, the use of three different classification systems developed by \nthe American Society of Reproductive Medicine (ASRM, 2006) [109], the European Society of Human \nReproduction and Embryology (ESHRE, 2013) and the  European Society for Gynecological Endoscopy \n(ESGE, 2013) does not permit to establish a  unique consensus about the prevalence of these \nmalformations [104]. Moreover, uterine anomalies are often asymptomatic and accidentally diagnosed \nduring ultrasounds for other  gynecological pathologies, assessment of tubal patency or pregnancy [110 \n111]. Moreover, they may also be recognized at delivery during spontaneous or cesarean section [112]. \nThe presence  of congenital uterine alterations represents a potential cause of infertility, recurrent \npregnancy loss, preterm delivery, fetal malpresentation as well as small -for-gestational age infants, with \ngreater effects being evident in women with more profound defects [113] \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 12 \n \nFig no 5:-uterian anomalies \nDiagnosis-As most CUAs are asymptomatic, the majority of them are detected incidentally.  A \nsignificant proportion of anomalies are diagnosed during fertility investigations. Accurate diagnosis and \ncorrect classification help in the appropriate counselling of women about their  potential reproductive \nprognosis and risks and for planning any intervention with a view to  improve the reproductive outcome. \nEvaluation of the internal and external fundal contours of the uterus is the key in making a diagnosis and \ncorrectly classifying a uterine anomaly.  Considering this, the gold standard test has been the combined \nlaparoscopy and hysteroscopy, albeit invasive, in the past. Imaging modalities such as ultrasonography, \nhysterosalpingogram (HSG), sonohysterogram and magnetic resonance imaging (MRI) are less invasive \nmodes of screening and classifying various uterine anomalies[113]. While conventional 2D tran svaginal \nultrasound (TVS) and HSG are considered as good screening modalities, 3D TVS and MRI  can \naccurately diagnose and classify the types of CUAs[114 115],  as they can  define both external and \ninternal uterine contours. \nENDOMETRIOSIS:- \nEndometriosis is defined as the presence of endometrial glands and stroma like lesions outside of the \nuterus[116]. The lesions can be  peritoneal lesions, superficial implants or cysts  on the ovary, or deep \ninfiltrating disease[117]. While there is no definitive etiology of endometriosis, there  are several \nhypotheses regarding how endometriotic lesions develop.  One possible mechanism  is retrograde \nmenstruation, a feature of the menstrual cycle in  women and non-human primates, which is an outflow \nof the endometrial lining thr ough the patent fallopian tubes into the pelvic space. This retrograde flow, \nalong with potential hematogenous or lymphatic circulation, may result in the seeding of endometrial \ntissue in  ectopic sites. However, retrograde menstruation is common (perhaps universal among \nmenstruating women) while endometriosis is much less common. Therefore, other factors,  such as \nhormonal, inflammatory, or immunologic milieu may determine whether lesions  deposited in the pelvic \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 13 \n \ncavity implant and persist [118–121]. Alternati vely, endometriosis lesions  may arise from Müllerian \nremnants that did not properly differentiate or migrate during fetal  development or from circulating \nblood cells that transdifferentiate into endometriosis [122–124]. Similarly, the characteristics of the local \nenvironment would influence the maintenance of  these endometriotic lesions. When considering these \netiologic hypotheses, it is important to  recognize that endometriotic lesions are antigenically similar to \neutopic endometrium but not necessarily endometrium. \nEndometriosis affects 10–15% of all women of reproductive age [116] and 70% of women with  chronic \npelvic pain [125]. Unfortunately, for many of these women there is often a delay in  diagnosis of \nendometriosis resulting in unnecessary suffering a nd reduced quality of life. In  patients aged 18–45 \nyears, the average delay is 6.7 years[126]. As most women with endometriosis report the onset of \nsymptoms during adolescence, early referral, diagnosis,  identification of disease and treatment may \nmitigate pain, prevent disease progression and  thus preserve fertility[127–129]. Barriers to early \ndiagnosis include the high cost of diagnosis and treatment in adolescent patients and presentation of \nconfounding symptoms such as  cyclic and acyclic pain. Thus, a non-invasive tool to diagnose \nendometriosis could facilitate earlier diagnosis and intervention that could ultimately improve quality of \nlife and preserve fertility \nFig no.6-Endometriosis \nMEDICAL INDUCTION \nPulsatile gonadotropin releasing hormone :-The pulsatile release of GnRH and LH plays an  important \nrole in the development of sex function and in the normal regulation of the menstrual cycle. In 1970, \nDierschke et al. first observed LH pulses in the ovariectomized  monkey[130]. Later studies also showed \nthis phenomenon in the human and rat. This LH pulse is produced by a corresponding GnRH pulse from \nthe hypothalamus [131]. Both the frequency  and amplitude of the GnRH pulse are critical for normal \ngonadotropin release [132]. One reason  for the GnRH secreti on in a pulsatile manner is to avoid the \ndown-regulation of the GnRH  receptor in the pituitary. In rhesus monkeys with hypothalamic lesions \nthat abolish pituitary  gonadotropin release, the constant infusion of exogenous GnRH fails to restore \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 14 \n \nsustained gonadotropin secration but intermittent administration of GnRH once per hour reestablishes  \ngonadotropin secretion[133]. Westel et al. showed that intrinsic pulsatile secretory activity was  seen in \nimmortalized GnRH neurons indicating that the pulse generator is cell autonomous[134]. Furthermore, it \nis known that the activity of each GnRH neuron is synchronized in vivo and immortalized GnRH \nneurons will spontaneously synchronize in  perfusion culture[135] Even though pulsatility of GnRH is \nrecognized as a major d eterminant for differential gonadotropin subunit gene expression and  \ngonadotropin secretion, very little is yet known about the signaling circuits governing GnRH action at \nthe pituitary level. In this  article, we review the current knowledge of the role of  pulsatile GnRH on \npituitary function and reproduction \nAntiestrogen treatment: clomiphene citrate -Two or 3 days after starting clomiphene  administration in \nthe follicular phase of the ovarian cycle, the pulse frequency of LH increases, suggesting that the main \naction of the drug is to increase pulsatile secretion of  gonadotrophin-releasing hormone (GnRH) by the \nhypothalamus (Sir et al., 1989).Clomiphene  could also have a direct oestrogenic effect on the \ngonadotrophs, enhancing sensitivity to GnRH. As a consequence of the effects mentioned above, there is \nan increase in plasma concentration of gonadotrophins and in the number of follicles recruited. There is \na resulting increase in plasma concentrations of oestradiol before ovulation and of progesterone durin g \nthe luteal phase. Between 30 and 35% of patients who ovulate with clomiphene do so with a  follicular \nrupture diameter that is larger than expected, as compared with spontaneous cycles.  Moreover, \nclomiphene has a direct oestrogenic effect on the ovary, re sembling that described  for the pituitary \ngland. It sensitizes granulosa cells in the follicle to the action of gonadotrophins and up-regulates \naromatase activity. Its effects on the cervix and endometrium are mainly anti-oestrogenic The different \nmodulating effects (agonistic or antagonistic) shown by clomiphene on the effectors of the genital tract \nmight be due to the  different populations of α - or β -oestrogen receptors in those tissues [136] \nClomiphene citrate induces ovulation in the majority of women. The ovulation rate ranges between 70% \nand 92%; however, the pregnancy rate is much lower. The discrepancy between the high ovulation rates \nand relatively low pregnancy rates may be due to the following factors: \n1. Antiestrogen effects on the endometrium \n2. Antiestrogen effects on the cervical mucus \n3. Decrease of uterine blood flow \n4. Impaired placental protein 14 synthesis \n5. Subclinical pregnancy loss 6.Effect on tubal transport \n6. Detrimental effects on the oocytes[199] \n \n \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 15 \n \nFig.no:7(A) Clomiphene citrate is available as a racemic mixture of two stereochemical isomers \nreferred to as (cis) Zu -clomiphene or the (trans) En -clomiphene confi guration, the former being signifi \ncantly more potent. In the preparations commercially available, the isomers are in the ratio of 38% Zu- \nand 62% En-clomiphene. 7(B) The isomeric models in a different confi guration. \n \nGonadotropins:- Patients remaining anovulatory [CC -resistant anovulation (CRA)] and  patients failing \nto conceive during CC treatment [CC failure to conceive (C CF)] are generally  treated with exogenous \ngonadotropins[137]. Recently, it has become more accepted to treat  CRA patients with a combination of \nCC and an insulin sensitizer before treatment with  exogenous gonadotropins is started. Individual \ndifferences in the daily amount of FSH required to induce ongoing follicle growth and ovulation (the \nFSH response dose) have been  suggested to be the main factor of hyper -responsiveness and severe \ncomplications during FSH ovulation induction[138]. This individual variat ion resulted in two different \napproaches in  ovulation induction with gonadotropins. The 'step -up' protocol aims at slowly and \nprudently surpassing the FSH -threshold to reduce the chances of these complications. However, this  \napproach might result in a prolonged treatment period and late follicular phase FSH accumulation, \nincreasing the risk of multifollicular growth. In an attempt to overcome these  problems, the 'step-down' \nprotocol has been developed, which mimics the physiological FSH  profile more closely[139]. The FSH \nstarting dose is presumed to be the response dose; hence,  dominant follicle growth is established more \nquickly. Thereafter, the FSH doses can be  reduced slowly,  resulting in the development  of a  single \ndominant follicle[139]. Frequent monitoring of the ovarian response is especially important during the \nstep-down protocol, because the duration of FSH threshold being suppressed determines whether there \nwill be mono-or multifollicular growth[140] . Stimulation is cancelled when multifollicular growth is \napparent and more than three follicles >12mm in diameter are present. \nMetformin:-This drug is used when insulin resistance is a known or suspected cause of  infertility, \nusually in women with a diagnosis of PCOS. Metformin (Fortamet) helps improve  insulin resistance, \nwhich can improve the likelihood of ovulation.Metformin is administered  orally and has an absolute \nbioavailability of 50–60%, and gastrointestinal absorption is \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 16 \n \napparently complete within six hours of ingestion. Metformin is rapidly distributed following  absorption \nand does not bind to plasma proteins. No metabolites or conjugates of metformin  have been identifi ed. \nMetformin undergoes renal excretion and has a mean plasma elimination half -life after oral \nadministration of between four and 8.7 hours. Food decreases  the extent of and slightly  delays the \nabsorption of metformin \nLetrozole:-Letrozole (Femara) belongs to a class of drugs known as aromatase inhibitors  and works in a \nsimilar fashion to clomiphene. Letrozole is usually used for woman younger than 39 who have PCOS. \nBromocriptine:-Bromocriptine (Cycloset, Parlodel), a dopamine agonist, might be used  when ovulation \nproblems are caused by excess production of prolactin (hyperprolactinemia) by the pituitary gland[141] \n \n \nMETHODS OF REPRODUCTIVE ASSISTANCE \nIntrauterine insemination (IUI) and ovarian stimulation are part of the initial management of couples \nwith infertility, known as low-complexity assisted reproductive technologies (ART). IUI requires basic \nsupplies and simple training, constituting a low -cost technique, accessible for the majority of couples. \nHowever, its effectiveness has  not been fully researched. Both, patients and the public in our country, \nbelieve IUI is very effective. Some researchers consider IUI as a trivial procedure for certain indications \nand recommend patients to go directly to high complexity ART[142]Others, point to it as a procedure \nwith potential complications, specifically associated with multiple pregnancies[143] \n \nFig no.8:-intrauterine insemination \nIntrauterine insemination involves careful coordination before the actual procedure \nPreparing the semen sample:-Your partner provides a semen sample at the doctor's  office, or a vial of \nfrozen donor sperm can be thawed and prepared. Because nonsperm  elements in semen can cause \nreactions in the woman's body that interfere with fertilization,  the sample will be washed in a way that \nseparates the highly active, normal sperm from lower  quality sperm and other elements. The likelihood \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 17 \n \nof achieving pregnancy increases by using a small, highly concentrated sample of healthy sperm. \nMonitoring for ovulation: -Because the timing of IUI is crucial, monitoring for signs of  impending \novulation is critical. To do this, you might use an at-home urine ovulation predictor kit that detects when \nyour body produces a surge or release of luteinizing hormone  (LH). Or, an imaging method that lets \nyour doctor visualize your ovaries and egg growth  (transvaginal ultrasound) can be done. You also may \nbe given an injection of human chorionic gonadotropin (HCG) or medications to make you ovulate one \nor more eggs at the right time. \nDetermining optimal timing:-Most IUIs are done a day or two after detecting ovulation. Your doctor \nor other care provider will have a plan spelled out for the timing of your procedure and what to expect. \n \nFig no.9:-transvaginal ultrasound \nINTRA UTERIAN INSEMINATION PROCEDURE:- \nOnce collected, the semen sample is then “washed” in the laboratory to concentrate the sperm  and \nremove the seminal fluid (seminal fluid can cause severe cramping in the woman). This  process can take \nup to 2 hours to complete.IUI is performed near the time that the woman is ovulating. The IUI procedure \nis relatively simple and only takes a few minutes once the semen sample is ready. The woman lies on an \nexamining table and the clinician inserts a  speculum into her vagina to see her cervix. A catheter \n(narrow tube) is inserted through the cervix into the uterus and the washed semen sample is slowly \ninjected. Usually this procedure  is painless, but some women have mild cramps. Some women may \nexperience spotting for a day or two after the IUI. \nIN VITRO FERTILIZATION \nTechniques that involve manipulation of oocytes outside the body are termed assisted reproductive \ntechnology (ART) with in vitro fertilization (IVF) as the most common form. The term „in vitro‟ means \noutside a living organism as  oocytes mature in vivo in the ovary  and embryos develop into pregnancy \nin the uterus, but the oocytes are fertilized in a petri dish.  Robert Edwards, Ph.D., and Patrick Steptoe, \nMD, reported the first live birth from  IVF in July 1978 in England. This achievement would later earn \nDr. Edwards the Nobel Prize in Medicine in 2010.[144] \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 18 \n \nFig.10:-IUI procedure \n \nSince this major breakthrough in the treatment of infertility, the field of reproductive \nendocrinology/infertility (REI) has progressed rapidly, and IVF now accounts for 1.6% and  4.5% of all \nlive births in the United States and Europe, respectively. [145] Initially developed as  a way to bypass \nirreparable tubal disease, IVF is now widely applied for the treatment of  infertility due to a variety of \ncauses, including endometriosis, male factor, and unexplained  infertility. Women who cannot use their \nown oocytes due to primary ovarian insufficiency  (POI) or age-related decline in oocyte number can \nnow become successfully pregnant utilizing donor oocyte IVF. \nTECHNIQUE \nControlled Ovarian Stimulation: -Complex endocrine changes happen while a woman  undergoes \novarian stimulation as part of IVF treatment. The two main aims of COS are: (a) to  create a cohort of \ndeveloping follicles; and (b) to prevent premature spontaneous ovulation. \nGnRH agonists are administered intramuscu larly, subcutaneously or intranasally. In the 'long  protocol', \nthe initial flare effect of the GnRH agonists is followed by desensitisation and  down‐ regulation of the \npituitary gland with an internalisation of the GnRH receptors. This  protocol is associate d with a higher \noocyte number and clinical pregnancy rates, but there is  evidence of an increase in the requirement of \ngonadotrophins compared to a 'short protocol[146]GnRH antagonists act by binding to the GnRH \nreceptors and prevent endogenous release of GnRH from the pituitary gland. GnRH antagonist protocols \nare associated with immediate LH suppression and decreased gonadotrophin use. As a result, antagonist \nprotocols are associated with a significant reduction in ovarian hyperstimulation syndrome  (OHSS) \nwithout reducing significantly the live birth rate[147] \nOocyte Retrieval:-A needle is passed through the top of the vagina under ultrasound  guidance to get to \nthe ovary and follicles. \nThe fluid in the follicles is aspirated through the needle and the eggs  detach from the follicle  wall and \nare sucked out of the ovary (see video above). \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 19 \n \nThe oocyte -cumulus complex is pulled from the follicle wall when we aspirate the fluid  through the \nneedle. The procedure usually takes about 10 minutes at our clinic The fluid with the eggs  is passed to \nthe IVF lab where the eggs are identified, rinsed in culture media, and placed  in small drops in  plastic \nculture dishes. The dishes with the eggs  are then kept in specialized IVF incubators under carefully \ncontrolled environmental conditions. \n \nEmbryo Fertilization:-When the fertilized egg divides, it becomes an embryo. Laboratory staff will \nregularly check the embryo to make sure it is growing properly. Within  about 5 days, a normal embryo  \nhas several cells that are actively dividing. \nCouples who have a high risk of passing a genetic (hereditary) disorder to a child may  consider pre-\nimplantation genetic diagnosis (PGD). The procedure is most often done 3 to 5  days after fertilization. \nLaboratory scientists remove a single cell or cells from each embryo  and screen the material for specific \ngenetic disorders. \nAccording to the American Society for Reproductive Medicine, PGD can help parents decide  which \nembryos to implant. This decreases the chance of passing a disorder onto a child. The  technique is \ncontroversial and not offered at all centers. \n \nEmbryo transfer -Embryos are placed into the woman's womb 3 to 5 days after egg  retrieval and \nfertilization.The procedure is done in the doctor's office while the woman is  awake. The doctor inserts a \nthin tube (catheter) containing the embryos into the woman's  vagina, through the cervix, and up into the \nwomb. If an embryo sticks to (implants) in the  lining of the womb and grows, pregnancy results.More \nthan one embryo may be placed  into the womb at the same time, which can lead to twins, triplets, or \nmore. The exact number of  embryos transferred is a complex issue that depends on many factors, \nespecially the woman's age.Unused embryos may be frozen and implanted or donated at a later date. \nFig no.11:-ivf process \n \n \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 20 \n \nINTRACYTOPLASMIC SPERM INJECTION(ICSI) \nintracytoplasmic sperm injection(ICSI) was introduced in 1992 to improve fertilization in  couples with \nmale factor infertility undergoing in vitro fertilization (IVF) or in couples with fertilization failure in a \nprior IVF cycle without detectable abnormalities of semen parameters  [148-150]. Although the \ndiagnostic criteria used to identify male factor infertility fail to predict  with perfect accuracy poor or \nabsent fertiliza tion in assisted reproductive technology (ART)  [151–154], studies to date support the \nsafety and efficacy of ICSI to treat various male factor  conditions. The use of ICSI for patients with \nborderline or even normal semen parameters has become more common[155 156] \nFig no.12:-intracytoplasmic sperm injection \n \nASSISTED REPRODUCTIVE TECHNOLOGY (ART) \nWhen couples do not achieve pregnancy from infertility treatments or traditional ART, they  may choose \nto use a third party–assisted ART method to get pregnant.[157] \nASSISTANCE CAN CONSIST OF: \n Sperm Donation \n Egg Donation \n Surrogates and Gestational Carriers \n Embryo Donation \nSPERM DONATION:-Assisted reproductive technology (ART) has become increasingly popular over \nthe past several decades. The advances in human sperm cryopreservation in the past 50 years and the \ncreation of sperm banks have facilitated the  increase in artificial insemination with donor sperm (AID) \n[158 159]. In cases of severe male  infertility, the use of donor sperm is the only approach to infertility  \ntreatment[160]Sperm donation is used for the artificial insemination with a third party donor (AID). The \ndonor becomes the biological father of the child, but he will not be considered the legal or social  father. \nAs a consequence, the child will have three parents, two fathers and a mother \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 21 \n \n \nFig no 13:-biological and legal relation of mother and father to child \nEGG DONATION:-The procedure typically involves a doctor removing an egg or eggs from the donor, \nfertilizing them in a laboratory, and then transferring the resulting embryos  into the recipient‟s uterus. \nDoctors do this using an implantation procedure, such as in vitro  fertilization (IVF).Sometimes, \nspecialists at the facility may freeze some or all of the embryos for later use or implantation in different \nwomen.Egg donation frequently benefits  women who cannot use their own eggs for various reasons, \nincluding ovarian failure, avoiding congenital anomalies in the fetus egg donation follows the steps of \nIVF treatment (till egg retrieval). The main difference  between IVF and egg donation is the role of \ndonor and the recipient. In the entire procedure of egg donation India, egg donor plays a vital role to \nachieve success.Without nourished and healthy eggs, the step of fertilization can‟t take place, and this is \nthe main reason, why donor  is tested in a comprehensive route. The entire procedure of egg donation \nIndia majorly depends upon egg donor.Fertility veterans of Egg Donation Clinic in India start giving \nfertility medication and hormonal injections to the donor.  The duration of this medication goes usually \n12-14 days. Fertility medication is given to the donor so that she will come up  with multiple eggs at the \ntime of egg retrieval or egg collection phase. Once the e ggs become fully matured, then with the help of \nhollow thin needle the eggs are picked up by the fertility  veterans of Egg Donation Clinic in India.Once \nthe eggs are taken out from the donor, the semen sample is collected from the recipient‟s male duo. Now \neggs and sperms are kept on the culture dish for fertilization, where motile sperm self penetrates with the \negg‟s wall and goes into the cytoplasm of the egg, resulting from cell division or fusion. Once the cells \nbegin to divide successfully, fertilization happens.After 3-4 days of fertilization, the healthiest embryo is \nchosen by the experts and then transferred into the uterus of the infertile female for  implantation. Now \nfrom here, recipient, that means infertile woman‟s role starts. Embryo  transfer ha rdly takes 35 -45 \nminutes for the completion and once the embryo is placed, a recipient can go back her home on the same \nday[161] \nFig no.14:-Egg donation process \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 22 \n \nSURROGATES AND GESTATIONAL CARRIERS:- \nThe word “surrogate” is rooted in Latin “Subrogare” (to substitute), which means “appointed  to act in \nthe place of.” It means a substitute, especially a person deputizing for another in a  specific role, so the \nsurrogate mother implies a woman who becomes pregnant and gives birth  to a child with the intention of \ngiving away this child to another person or couple, commonly  referred to as the  “intended” or \n“commissioning” parents[162] \nThe surrogate embryo transfer could be fresh or frozen transfer and subject to availability of  the \ngestational carrier. With advent of excellent vitrification techniques, surrogacy cycles have become less \ndifficult for assisted reproductive technology  (ART) clinic with good  embryology laboratory and \nfreezing facility.For a fresh surrogate transfer, the surrogate and the intended mother cycle may be \nsynchronized with oral contraceptive pills or progesterone  pills or surrogate may be put on agonist \ninjection for flexibility of transfer dates.The surrogate is started on estrogen tablets from the 3rd day of \nher cycle for around 10 days. On  reaching of minimum 8 mm, she is then put on progesterone \nsupplementation for 3 days/5 days before a planned cleavage stage/blastocyst transfer, respectively \n \nCARE OF SURROGATE \nOnce a pregnancy is confirmed in the gestational carrier depending on the facility of the  ART clinic, \nshe either stays in the surrogate house or at her home. The concept of surrogate  house has recently \ncaught a lot of attention for various reasons. Surrogate house is a place  where surrogate stays for her \nentire antenatal period till the date of delivery and all her medical and pers \nonal requirements are taken care of. The obstetrics care of surrogate is extensive due to the  preciousness \nof the pregnancy. She stays under the supervision of 24 -h nursing staff alon g with dietician, \nphysiotherapist, counselors, and gynecologist for her medical care. It is due to  this care and available \nfacilities that intended couples have taken up more liking towards the  concept of surrogate house. \nAlthough staying at surrogate house is preferred practice these days, considering the other side of coin, it \ncould be emotionally taxing for surrogate and her  entire family as she has  to live away  from her own \nchild/children and family; however, during their stay at surrogate house, surrogate can go home for few \nweeks during pregnancy  and her family members can also visit her at surrogate house. Staying at \nsurrogate house should be optional and not compulsion for surrogate mother and she should be given a \nchoice. \nSurrogates undergo obstetrics assessment every 20 days till the date of delivery, obstetrics  scans at 6–8 \nweeks, anomaly scan at 11 –13 weeks, anomaly scan and 3D -4D at 20–22 weeks, and growth scan at 28 \nweeks and 34–36 weeks. Any additional scan is subject to the obstetric need. \nThe intended couple is sent regular update regarding the surrogate's pregnancy in the form of  her weight \ngain, vitals, fetal growth, and antenatal investigation reports and scans. Postdelivery, the surrogate  is \nkept under observation for a minimum of 15 days before discharge \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 23 \n \nRISKS ASSOCIATED WITH SURROGACY \nThe major risk associated with surrogacy is that of obstetrics complication and multiple order  pregnancy \nbeing the most common. Recently, lot of recommendations are being made by  American Society for \nReproductive Medicine (ASRM) and European Society of Human  Reproduction and Embryology \ncommittees for single embryo transfer, but yet only 15% –20% of clinics follow single embryo transfer \nnorms.[163] Pregnancy, birth, and the postpartum  period includes complications such as preeclampsia \nand eclampsia, urinary tract infections,  stress incontinence, and gestational diabetes and rare \ncomplications such as amniotic fluid  embolism and possibility of postpartum hemorrhage,  but these  \nrisks are associated with pregnancy in general and not specific to surrogacy. \nApart from physical risk, surrogacy may be reason for emotional trauma as the study by  Foster (1987) \nstates that many surrogate mothers face emotional problems after having to  relinquish t he child. \nHowever, a study by Jadva et al.[164] indicates that although some women  experience emotional \nproblems in handing over the baby, these feelings appeared to lessen  during the weeks following the  \nbirth.[164] \nFig no.15:-Timeline of surrogacy process \n \nEMBRYO DONATION \nIn the current practice of in vitro fertilization (IVF), some patients may create more embryos  (fertilized \neggs) than they need. The extra embryos may be cryopreserved (frozen) so that they can be transferred \nlater. However, sometimes these embryos may not be used. These  patients have the option to have their \nembryos discarded, donated to research or donated to another woman to achieve pregnancy.[165] \n\n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 24 \n \nMISCARRIAGE AFTER FERTILITY TREATMENT \nMiscarriage is common, with a rate of between 10% and 30% of all spontaneous \npregnancies[174]Infertility is also common, affecting about 15% of couples.[175] The causes of \ninfertility are  multiple and  diverse yet  some, for  example endometriosis  and the  polycystic ovary \nsyndrome (PCOS) may also affect successful implantation and pregnancy outcome. With the \ndevelopment of assisted conception it is now possible to overcome or circumvent many of the \nproblems presented by the subfertile  couple. The main questions arising  from the various therapies \navailable are: do they increase the rate of miscarriage or fetal malformations?  by examining both the \ninfluence on miscarriage of the drugs used in ovulation induction and the effect of the different \ntechniques employed in assisted conception. First it is important to consider special factors that pertain \nto miscarriage in the infertile couple. \n \nTHE INFLUENCE ON MISCARRIAGE OF THE DRUGS USED IN FERTILITY THERAPY \nOvulatory failure accounts for about a fifth of cases of infertility. Over the last 30 years drug  regimens \nof increasing complexity have evolved to induce ovulation. The drugs prescribed to  anovulatory women \nare also used to induce multifollicular growth in women who ovulate  normally. These women benefit \nfrom superovulation as the production of several oocytes  increases the success of assisted conception \ntherapies. The most commonly used preparations  are the anti -estrogens (e.g. clomifene citrate), the \ngonadotropins and gonadotropin-releasing hormone analogs . Information about the sequelae of the use \nof fertility drugs therefore chiefly refers to these three groups \nANTI-ESTROGENS \nThe most widely prescribed anti -estrogen is clomifene citrate. Its use in ovulation induction  was first \nreported by Greenblatt et al[176] at a time when human pituitary and menopausal urinary gonadotropins \nwere also beginning to be extracted and standardized. In an early report of pregnancy outcome in a \nsmall number of women, Greenblatt et al found the incidence of spontaneous abortion to be 22%.[177] \nKarow and Payne[178] reported on a heterogeneous group of 410 infertile  women, in whom a \npregnancy rate of 39.8% was achieved. The spontaneous abortion rate was 19%, similar to that seen in \ninfertility patients prior to the advent of the drug. The inciden ce of twins was 8.6%, contributing to a \npremature delivery rate of 12%. There was no confirmation of an earlier theory that conception in the  \nfirst treatment cycle resulted in an increased chance of miscarriage or multiple pregnancy.  Also in 1968, \na series of 2196 clomifene -induced pregnancies was reported, [179] in which the  miscarriage rate was \n17.6%, the multiple pregnancy rate 10.2%, and the incidence of congenital anomalies 2.5%. Although \nclomifene was found to induce ovulation in about 90%  of infertile women and pregnancy in 50%, the \nmultiple pregnancy rate was sometimes as high  as 50%. In general the miscarriage rate after clomifene \ntreatment has been reported to be  between 20% and 27%, the rate of multiple pregnancy 10–15%, and \nthe incidence of congenital abnormalities about 2–3%.[180-182] One series reported an overall \nmiscarriage rate of 9.3%, 28.1% if conception occurred during the first cycle of treatment, and as high as \n70% if conception resulted after seven cycles. It was thought that  prolonged usage of clomifene  might \nhave a deleterious effect on the endometrium, causing atrophy and implantation failure.  The relatively \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 25 \n \nhigh miscarriage rate during the first cycle of treatment that was seen in this  study was postulated as \nbeing secondary to the  release of “overripe” oocytes after a prolonged period of anovulation. \nInterpreting data from the early use of clomifene is complicated by the lack of uniformityin  presenting \ndetails of maternal age and the cause of infertility. Monitoring was li mited to measurement of urinary \nestrogens or vaginal cytology and often omitted. Pregnancy diagnosis was not as advanced as at present \nand so it is inappropriate to compare miscarriage  data between the different series. Most women who \nrequire clomifene to induce ovulation have PCOS and are likely to have a tendency to hypersecrete LH. \nClomifene achieves its  action through stimulation of both follicle stimulating hormone (FSH) and LH \nsecretion by the pituitary and women with PCOS can respond with an exaggera ted release of LH and a  \nresultant reduction in the chance of conception and increase in the risk of miscarriage.[183] \nCONGENITAL ABNORMALITIES WITH CLOMIFENE CITRATE \nThe risk of congenital abnormalities and the physical development of infants born to mothers who have \nreceived clomifene has not been found to be different to that of the general population, yet concern was \nexpressed about the finding of an increased frequency of chromosomal abnormalities after induced \novulation,[184] an effect that appeared to persist during the subsequent, non-stimulated cycle. Following \nthe report of two cases of neural tube  defects after clomifene therapy, [185] other isolated cases of \ncongenital abnormalities appeared in the literature. Most have felt that factors relat ed to infertility itself \nmay be to blame, rather  than ovulation induction, and that babies born after ovulation induction are no \nmore at risk of  being malformed than if they were conceived spontaneously. [186]Whereas there \ncontinue to be  reports that suggest a more than coincidental association between ovulation induction, \nspecifically using clomifene, and neural tube defects, [187] other reports are reassuring and  suggest no \nevidence for this.[188] Shoham et al reviewed  3751 births after clomifene ther apy and found an overall \nincidence of major and minor malformations of 32.5 per 1000 births,1  this figure being within the range \nfound among the normal population.[186] \nOVULATION INDUCTION WITH GONADOTROPINS \nWomen who do not respond to oral therapy may succeed in having ovulation induced with gonadotropin \ntherapy. The preparations available either contain both LH and FSH or contain  FSH alone . It was \nthought that the use of FSH alone would benefit women with the PCOS by  minimizing circulating LH \nlevels. However, these women are usually very sensitive to both  forms of treatment and the use of FSH \nalone confers no advantage as serum concentrations of  LH are still within the normal range when human \nmenopausal gonadotropin (hMG) is used.  The amount of LH in hM G preparations is small compared \nwith the amount secreted by the pituitary and so is rapidly diluted after administration; furthermore, with \nunifollicular ovulation induction the developing follicle secretes hormones that feed back to the \nhypothalamus and pituitary and suppress endogenous LH secretion. Studies to date indicate  that \nmiscarriage rates are similar irrespective of the gonadotropin used. \nAs for the actual reported miscarriage rate after gonadotropin -induced ovulation, this varies  between \n11.3% and 27.5%. Lunenfeld et al also reported an analysis of the abortion rates in  both the first and \nsubsequent treatment cycles and the first and subsequent pregnancies.[189]Miscarriage after fertility \ntreatment In this study it was found that whereas the  abortion rate was 28.8% in a first pregnancy,  it was \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 26 \n \nonly 12.8% in a second pregnancy. This  figure is similar to the 13% of women  who aborted after a \nspontaneous conception that  followed a successful gonadotropininduced pregnancy. There was no \ndifference in the abortion rates of patients who became pregnant after the first or subsequent treatment \ncycles. This goes against a commonly proposed theory that anovulatory women release eggs of “poor  \nquality” in their first  ovulation induction cycle.[190]Other grou ps have also found a higher  miscarriage \nrate in the first gonadotropin-induced pregnancy. One series reported a reduction in miscarriage rate \nfrom 28.5% in first hMGpregnancies to 11.9% in those conceiving for a  second time;[190]another series \nfound these figures to be 33% and 9.8%, respectively.[191] In  contrast to these studies, a more recent \npaper reported an overall spontaneous abortion rate in  350 pregnancies after first treatment cycles of \n24.2%, yet a 48% abortion rate in a subsequent  pregnancy in women whose first hMG pregnancy ended \nin a spontaneous abortion; this  compared to an incidence  of abortion of 6.7% if the first hMG -induced \npregnancy was  normal.[192]These data are in keeping with the notion that the risk of miscarriage \nfollowing a  natural c onception is directly related to a woman‟s past obstetric history. We reported a  \nretrospective analysis of all patients treated in the ovulation induction clinic at the Middlesex  Hospital, \nLondon, from May 1982 to January 1993. [193] A total of 200 anovulatory patients were included in the \nanalysis, 103 with clomifene citrate-resistant PCOS, 77 with hypogonadotropic hypogonadism (HH), \nand 20 with weight-related amenorrhea (WRA). There was no difference in the mean age of the three \ngroups. The cumulative conception rates  (CCR) and cumulative live birth rates (CLBR) of the three \ngroups in the first course of  therapy and after 12 cycles of treatment are illustrated in The miscarriage \nrates were 16.5% in  PCOS patients, 22.9% in HH patients, and 32.3% in WRA patients and, while not \nstatistically significantly different, this resulted in comparable CLBRs between the three groups. Patients \nwith amenorrhea secondary to weight loss respond well to ovulation induction therapy with normal or \nsupranormal cumulative conception rates.[194-196]The miscarriage rate in these patients, however, was \n32% and this resulted in a cumulative live  birth rate that was similar to that of patients with PCOS and \nHH. Furthermore, women who  conceived spontaneously and had a body mass i ndex (BMI) of less than \n19.1 kg/m2 had twice  the risk of delivering a low birthweight infant compared with women of normal \nweight (p < 0.005)[197] and they also had a higher incidence of preterm deliveries (p < 0.01). We have \nalso reported previously that patients with WRA who conceive after treatment  with pulsatile  \ngonadotropin releasing hormone (GnRH) are more likely to deliver lighter babies than of  normal weight \n(p < 0.001).[198] Our current approach is therefore to encourage weight gain and not to induce \novulation in women with a BMI of less than 19.5 kg/m2. \nVIRAL DISEASE AND ASSISTED REPRODUCTIVE TECHNIQUES \nHIV-positive women  need to address a number  of issues when  planning to conceive.  The HIV \nphysician is best placed to provide pre -conceptual advice on HAART, self -insemination methods, and \nmeasures that will need to be put in place during pregnancy to reduce MTCT  risk, as well as advising on \nany long -term health issues related to viral illness, which might be  a contraindication to pregnancy.  \nRelatively few antiretroviral medications (e.g., Efavirenz)  are contraindicated during pregnancy due to \npotential teratogenic effects on the fetus [200]but it  should be borne in mind that the evidence on the \nsafety of most antiretrovirals during pregnancy is still incomplete. Folic acid should be given antenatally \nto minimize the risk of  neural tube defects as antiretrovirals are known to have a folate antagonist \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 27 \n \neffect.There is  increasing evidence to suggest that HIV -positive women have reduced  fertility[201-\n202]There are no data to suggest an increased incidence of cycle irregularity in positive women, but  \nstudies on positive women undergoing IVF suggest that HIV -positive women have lower IVF  success \nrates than HIV-negative controls and require higher doses of gonadotropin stimulation [203-205]. IVF \noutcome does not appear to be affected in HIV -positive women  undergoing ovum donation, pointing \ntoward an effect of HIV and/or immunosuppression on  ovarian response and ovarian reserve rather than \non implantation [206]. Retrospective  data from Sub -Saharan Africa [207 -208] and prospective data \nfrom the United Kingdom indicate an  increased incidence of tubal infertility in positive women [201 -\n202] of at least twice that of HIV- negative controls. On the basis of increased risk of low ovarian reserve \nand increased tubal infertility, HIV-positive women trying to conceive should be referred sooner rather \nthan later for fertility evaluation and certainly if they have not conceived within six to 12 months of self-\ninsemination. Referral should be early if there is a history of pelvic infl  ammatory disease or in women \nover 35 years of age to assess tubal function and ovarian reserve. \nREDUCING RISK DURING ART IN POSITIVE WOMEN \nMinimizing risk in HIV -positive women lies primarily in reducing MTCT. There are no  additional \nspecific measures that can be taken during fertility treatment to further reduce this  risk. There has been \nconcern that invasive procedures such as IVF could increase the chances  of the embryo becoming \ninfected. The number of women treated so far is small and prospective data limited. A study of 10 \nwomen undergoing IVF or ICSI demonstrated that  HIV was detectable in follicular fluid removed \nduring vaginal egg collection in all patients  with a detectable se rum VL and in 60% of those with an \nundetectable serum VL [209]. This raises the theoretical possibility of the embryo becoming infected at \nthe laboratory stage of  ART even before embryo transfer, although the likelihood is that viral infection \nwould lead t o embryo death. Longitudinal studies are needed to monitor outcome of ART cyclesin \npositive women to identify if any such risk increases the chance of MTCT.Management of HIV- positive \nwomen should involve a multidisciplinary team comprising HIV physician, fertility specialist, and \nobstetrician with a special interest in HIV. The couple should have a sexual  health screen for the same \nreasons as couples undergoing sperm washing. Likewise they  should have a fertility screen in a similar \nway to HIV -negative cou ples (early follicular phase  endocrine profile and pelvic scan, mid -luteal \nprogesterone, and test of tubal function) and the  male partner should have a semen analysis[210]. \nCouples concordant for HIV should be advised to conceive using sperm washing to prevent the risk of \nsuperinfection. \n \nMANAGING PATIENTS WITH HEPATITIS \nHepatitis B (HBV) and Hepatitis C (HCV) viruses are major causes of chronic hepatitis,  cirrhosis, and \nhepatocellular cancer. In cases where fertility treatment is required and one or  both partners are HBV or \nHCV positive, samples should be treated as infectious and handled  according to clinical and laboratory \nguidelines set out below.In the case of hepatitis B, vertical transmission accounts for over 40% of cases \nof chronic infection a nd the sexual transmission risk is twofold higher than for HIV  and sixfold higher \nthan for HCV. Unlike  HIV or HCV, an effective vaccine is available for HBV and all healthcare \nworkers and  partners of known infected individuals should be vaccinated. Uninfec ted women should \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 28 \n \nonly consider conception post -vaccination. Sperm washing should not be required as a means of  \nreducing horizontal transmission risk unless a woman fails to develop adequate immunity  through \nvaccination. If ART is required in HBV positive c ouples for fertility issues, similar  clinical protocols to \nnon-infected patients should be used. The Dutch view, as with HIV samples, is that if ART is required in \na couple where the male is HBV positive, ICSI should  be avoided due to the risk of introduci ng HBV \ninto the oocyte [211]. There are no substantive data to support this view.Vertical transmission risk for an \nHBV positive woman during  pregnancy is 2 –15% if she is only HBsAgpositive, and 80 –90% if she is \nalso positive for  HBeAg or is HBV DNA positive. Infection in the neonate can be minimized if \nimmunoprophylaxis (HBV vaccination and one dose of Hepatitis B immunoglobulins) is  given within \n24 hours of birth with a further dose at one and six months. Breastfeeding does  not appear to play a role \nin perinatal transmission.HCV infection is primarily transmitted by  parenteral spread (blood products, \nshared needles, needlestick injury). Sexual transmission risk is very low unless the patient is co -\ninfected with HIV [212]. There is no vaccine for HCV  and sperm washing should be offered to \nHCVdiscordant couples where the male is infected.  The principles of treatment are the same as in HIV -\ninfected discordant couples[213,214] and  sperm washing is as effective in reducing transmission risk to \nthe female  partner as in  discordant cases of  HIV. Patients who have expressed a desire to become \nparents, but who are in a high -risk group for  infertility based on their age, should have a basic fertility \nevaluation and be referred to a  specialist in a timely manner in order to maximize their fertility \npotentiaInfertility may work  as a painful emotional experience[166 167]. It can cause a lot of \npsychological issues including  stress, anxiety, depression, diminished self -esteem, declined sexual \nsatisfaction, and reduced quality of life[168,169,170]. The resulted psychosocial issues affect the female \ngender adversely more than her spouse [171], especially in societies where there are prejudices against \nwomen[169 170 172] . As such, an infertile woman may show a relatively  high level of frustration  and \nanger which affect her relationship with family, friends and even her spouse. Likewise,  infertile women \nare more likely to develop  mental illnesses, marital  dissatisfaction, and  impaired quality of  life \ncompared to the individuals of fertile group[169, 172 173]. \nCONCLUSION \nMany women have reported finding treatment for infertility stressful and a cause of relationship \ndifficulties with their partners. The fear of failure was the most important barrier  to treatment. The \npsychological support is fundamental to limit the possibility to drop -out from infertility treatment and \nreduce the distress level which is strongly associated with lower  pregnancy rates. In addition some \nmedications used in the treatment have several side  effects which may be an important risk factor for the \ndevelopment of depression Many infertile  women tend to cope with immense stress and social stigma \nbehind their condition, which can  lead to considerable mental distress.The long -term stress involved in  \nattempting to conceive a child and the social pressures behind giving birth can lead to emotional distress \nthat may manifest as mental disease.Women with infertility might deal with psychological stressors such \nas denial, anger, grief, guilt, and depressi on.There can be considerable social shaming  that can lead to \nintense feelings of sadness and frustration that potentially contribute to  depression and suicide.The \nimplications behind infertility bear huge consequences for the  mental health of an infertile woman \nbecause of the social pressures and personal grief behind being unable to bear children \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 29 \n \nACKNOWLEDGEMENT \nI express heartfelt gratitude to Dr. Rajesh Oswal and Prof Diksha Gupta, of Genba Sopanrao  Moze \nCollege of Pharmacy , Wagholi for their full guidance and also for providing digital library. \nREFERENCES \n \n1. GUTTMACHER AF. Factors affecting normal expectancy of conception. J Am Med Assoc. \n1956 Jun 30;161(9):855-60. \n2. Infertility Workup for the Women's Health Specialist: ACOG Committee Opinion, Number 781. \nObstet Gynecol. 2019 Jun;133(6):e377-e384. \n3. Valoriani VFL, Lari D, Miccinesi G, Vaiani S, Vanni C, Coccia ME, et al. Differences in \npsychophysical well-being and signs of depression in couples undergoing their first  consultation \nfor assisted reproduction technology (ART): an Italian pilot study. Europ J Obstet Gynecol Reprod \nBiol. 2016;197:179–185. \n4. Veltman-Verhulst S. Emotional distress is a common risk in women with polycystic  ovarian \nsyndrome: a systematic review and meta -analysis of 28 studies. Hum Repr od Update. \n2012;18(6):638–651. doi: 10.1093/humupd/dms029. \n5. Gokhan A. Level of anxiety, depression, self esteem, social anxiety, and quality of life  among \nwomen with polycystic ovarian syndrome. Sci World J. 2013;2013:7. \n6. Jedel E. Anxiety and depression symptoms in women with polycystic ovarian syndrome  compared \nwith controls matched for body mass index. Hum Reprod. 2009;25(2):450– \n7. 456. doi: 10.1093/humrep/dep384. \n8. Baldur-Felskov P. disorders in women with fertility problems: results from a large  Danish    \nregister-based     cohort     study.     Hum     Reprod.     2013;28(3):683 –690. doi: \n10.1093/humrep/des422. \n9. Wendy Kuohung, Mark, D. Hornstein, Robert, L. Barbieri, Vanessa, A. Barss. (2009):  Evaluation \nof female Infertility; 2009, version 17.3 \n10. JLH Evers, JA Collins. Lancet, 2003, 361: 1849-52 \n11. SO Ogunniyi, OO Makinde, and FO Dare. African Journal of Medicine and Medical  Science, \n1999, 19(4): 271 – 274.. \n12. OA Esimai, EO Orji, AR Lasisi. Niger J Med., 2002, 11:70-72 \n13. MC Inhorn. Social Science and Medicine, 1994a, 39, 4:459-461. \n14. OO Adetoro, and EW Ebomoyi. African Journal of Medicine and Medical Sciences,  1991, \n20,1:23-7. \n15. Barton D. The Natural Guide to Infertility and Depression. 2014. Natural Fertility Info.com, 2014 \n16. Bartholow L. Stress, Trauma & Depression Talk. Portland Plant Medicine Gathering. 2012. \n17. Akker O. Coping, Quality of Life and Psychological Symptoms in Three Groups of Sub - Fertile \nWomen. Patient Educ Couns. 2005;57:183 –189. doi: 10.1016/j.pec.2004.05.012.  \nhttp://www.ncbi.nlm.nih.gov/pubmed/15911191. \n18. Chachamovich J, Chachamovich E, Zachia S, Knauth D,Passos E. What Variables Predict Generic \nand HealthRelated Quality of Life In A Sample of Brazilian Women Experiencing Infertility? Hum \nReprod. 2007;22:1946–1952. doi: 10.1093/humrep/dem080. http://www.ncbi.nlm.nih.gov/ \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 30 \n \npubmed/17428881. \n19. Wischmann T, Stammer H, Scherg H, Gerhard I, Verres R. Psychosocial Charac teristics of \nInfertile Couples: A Study by the Heidelberg Fertility Consultation Service. Hum  Reprod. \n2001;16:1753–1761. doi: 10.1093/humrep/16.8.1753. \n20. Nelson C, Naughton C, Ohebshalom M, Mulhall J.Sexual Function and Quality Oo Life  in The  \nMale Partner of Infertile Couples: Prevalence and Correlates of Dysfunction. J  Urol. 2008; \n179:1056–1059. doi: 10.1016/j.juro.2007.10.069. \n21. Fassino S, Piero A, Boggio S, Piccioni V, Garzaro L.Anxiety, Depression and Anger  Suppression \nin Infertile Couples: A Controlled Study. Hum Reprod. 2002;17:2986 –2994. doi: \n10.1093/humrep/17.11.2986. \n22. Inhorn M. Global Infertility and The Globalization of New Reproductive Technologies:  \nIllustrations from Egypt. Soc Sci Med. 2003;56:1837–1851. doi: 10.1016/S0277- 9536(02)00208-\n3. \n23. Orji E, Kuti O, and Fasubaa O. Impact of Infertility on Marital Life in Nigeria. Int J  Gynaecol \nObstet. 2002;79:61–62. doi: 10.1016/S0020-7292(02)00180-7. \n24. Paolo T. Clinical Management of Male Infertility: Prevalence, Defifi- nition, and Classifification \nof Infertility. Springer; 2015; 5-11. \n25. McKinney E, James S, Murray S, et al. Maternal Child Nursing. Saunders: Elsevier, Canada. 2009; \n202. \n26. Wheaton B. The twain meet: distress, disorder and the continuing conundrum of categories \n(comment on Horwitz). Health. 2007;11: 303-319. http://dx.doi.org/10.1177/1363459307077545 \n27. Mirowsky J, CE. Ross. Selecting outcomes for the sociology of mental health: Issues of  \nmeasurements and dimensionality. J Heal Soci Behavi. 2002; 43: 152-170. PMid:12096697 \nhttp://dx.doi.org/10.2307/3090194 \n28. Hamilton-Fairley D, Taylor A. ABC of subfertility: Anovulation. BMJ. 2006;327:546– 549 \n29. Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. \n2003;14:365–370 \n30. Panidis D, Farmakiotis D, Kourtis A, Rousso D. Resistin as a local factor in polycystic  ovary \nsyndrome: a novel view of \"adipo(cyto)kines\"? Hum Reprod. 2004;19:1681– 1682. \n31. Panidis D, Balaris C, Farmakiotis D, et al. Serum parathyroid hormone concentrations are \nincreased in women with polycystic ovary syndrome. Clin Chem. 2005;51:1691– 1697 \n32. Panidis D, Farmakiotis D, Koliakos G, et al. Comparative study of plasma ghrelin levels  in women \nwith polycystic ovary syndrome, in hyperandrogenic women and in normal  controls. Hum Reprod. \n2005;20:2127–2132 \n33. Panidis D, Farmakiotis D, Rousso D, Katsikis I, Kourtis A, Diamanti -Kandarakis E.  Serum \nluteinizing hormone levels are markedly increased and sig nificantly correlated  with Delta 4-\nandrostendione levels in lean women with   polycystic   ovary syndrome. Fertil Steril. \n2005;84:538–540 \n34. Hughesdon PE. Morphology and morphogenesis of the Stein -Leventhal ovary and of so - called \n'hyperthecosis'. Obstet Gynecol Surg. 1982;37:59–77 \n35. Webber LJ, Stubbs S, Stark J, et al. Formation and early development of follicles in the  polycystic \novary. Lancet. 2003;362:1017–1021 \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 31 \n \n36. Jonard S, Dewailly D. The follicular excess in polycystic ovaries, due to intra -ovarian \nhyperandrogenism, may be the main culprit for the follicular arrest. Hum Reprod Update. \n2004;10:107–117 \n37. Ehrmann D. Polycystic ovary syndrome. N Eng J Med. 2005;352:1223–1236 \n38. Azziz R, Ehrmann D, Legro RS, Whitcomb RW, Hanley R, Fereshetian AG. Troglitazone \nimproves ovulation and hirsutism in the polycystic ovary syndrome: a multicenter,    double    \nblind,    placebo-controlled    trial.    J     Clin     Endocrinol Metab. 2001;86:1626–1632 \n39. Panidis D, Farmakiotis D, Rousso D, et al. Obesity, weight loss and the polycystic ovary syndrome: \neffect of treatment with diet and orlistat for 24 weeks  on insulin resistance  and androgen levels. \nAm J Clin Nutr. 2006:in–press. \n40. Greenblatt RB, Bafrield WE, Jungck EC, Ray AW. Induction of ovulation with MRL/41.  \nPreliminary report. J Am Med Assoc. 1961;178:101–104 \n41. Homburg R, Insler V. Ovulation induction   in   perspective.   Hum   Reprod  Update. \n2002;8:449–462 \n42. Hoek A, Schoemaker J, Drexhage JA. Premature ovarian failure and ovarian autoimmunity. End \nRew. 1997;1:163–169 \n43. Starup J, Sele V. Premature ovarian failure. Acta Obstet Gynecol Scand. 1973;52:259– 268 \n44. Alper MM, Garner PR. Premature ovarian failure: its relationship to autoimmune diseas. Obstet \nGynecol. 1985;66:27–30 \n45. Philip J,  Sele V, Trolle  D. Secondary hypergonadotrophic amenorrhea. Acta Obstet Gynecol \nScand. 1966;45:142–147. \n46. Sele V, Starup J. Premature ovarian failure. Acta Obstet Gynecol Scand. 1971;50:24 \n47. Zarate A, Karchmer S, Gomez E, Castelazo -Ayala L. Premature menopause. A clinical, histologic, \nand cytogenetic study. Am J Obstet Gynecol. 1970;106:110–114 \n48. Turner HH. A syndrome of infantilism, congenital webbed neck, and cubitus valgus.  \nEndocrinology 1938; 28:566 \n49. Z Kinderheilk. Über typische Kombinationsbilder multipler Abartungen. Eur J Pediatr  1930; \n49:271 \n50. Bondy CA, Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a \nguideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab 2007; 92:10. \n51. Cockwell A, MacKenzie M, Youings S, Jacobs P. A cytogenetic and molecular study of a series \nof 45,X fetuses and their parents. J Med Genet 1991; 28:151. \n52. Nielsen J, Wohlert M. Chromosome abnormalities found among 34,910 newborn children: results \nfrom a 13-year incidence study in Arhus, Denmark. Hum Genet 1991; 87:81. \n53. Gunther DF, Eugster E, Zagar AJ, et al. Ascertainment bias in Turner syndrome: new insights from \ngirls who were diagnosed incidentally in prenatal life. Pediatrics 2004; 114:640. \n54. Baena N, De Vigan C, Cariati E, et al. Turner syndrome: evaluation of prenatal diagnosis  in 19 \nEuropean registries. Am J Med Genet A 2004; 129A:16 \n55. Iyer NP, Tucker DF, Roberts SH, et al. Outcome of fetuses with Turner syndrome: a 10 - year \ncongenital anomaly register based study. J Matern Fetal Neonatal Med 2012; 25:68. \n56. Hassold T, Pettay D, Robinson A, Uchida I. Molecular studies of parental origin and  mosaicism in \n45,X conceptuses. Hum Genet 1992; 89:647. \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 32 \n \n57. Romero ST, Geiersbach KB, Paxton CN, et al. Differentiation of genetic abnormalities in  early \npregnancy loss. Ultrasound Obstet Gynecol 2015; 45:89. \n58. Levy B, Sigurjonsson S, Pettersen B, et al. Genomic imbalance in products of conception:  single-\nnucleotide polymorphism chromosomal microarray analysis. Obstet Gynecol 2014; 124:202. \n59. Azmanov DN, Milachich TV, Zaharieva BM, et al. Profile of chromosomal aberrations in \ndifferent gestational age spontaneous abortions detected by comparative genomic hybridization. \nEur J Obstet Gynecol Reprod Biol 2007; 131:127. \n60. Eiben B, Bartels I, Bähr-Porsch S, et al. Cytogenetic analysis of 750 spontaneous abortions with \nthe direct-preparation method of chorionic villi and its implications for  studying genetic causes of \npregnancy wastage. Am J Hum Genet 1990; 47:656. \n61. Chernausek SD, Attie KM, Cara JF, Rosenfeld RG, Frane J. Growth hormone therapy of  Turner \nsyndrome: the impact of age of estrogen replacement on final height. Genentech,  Inc., \nCollaborative Study Group. The Journal of clinical endocrinology and metabolism.  \n2000;85(7):2439-45. \n62. Attar AF, Mousavi P, Javadnoori M, Malehi AS. The Relationship betwee n Gynecologic Age and \nMaternal/Fetal Weight Gain in Adolescent Pregnancies. J. Biochem. Tech. 2019;10(3):50-5. \n63. Bondy CA, Bakalov VK. Investigation of cardiac status and bone mineral density in  Turner \nsyndrome. Growth hormone & IGF research : official journ al of the Growth  Hormone Research \nSociety and the International IGF Research Society. 2006;16 Suppl A:S103-8. \n64. Hindmarsh PC, Dattani MT. Use of growth hormone in children. Nature clinical practice  \nEndocrinology & metabolism. 2006;2(5):260-8 \n65. Badawy A, Elnashar A. Treatment options for polycystic ovary syndrome. International  Journal of \nWomen‟s Health. 2011;3:25. DOI: 10.2147/IJWH.S11304 \n66. Legro RS, Dodson WC, Kunselman AR, et al. Benefit of delayed fertility therapy with  \npreconception weight loss over immediate  therapy in obese women with PCOS. The  Journal of \nClinical Endocrinology and Metabolism. 2016;101:2658-2666. DOI: 10.1210/jc.2016-1659 \n67. Biller BM, Luciano A, Crosignani PG, Molitch M, olove D, Rebear R, et al. Guidelines  for the \ndiagnosis and treatment of hyperprolactinemia. J Reprod Med.1999;44(Supp112):1075-84 \n68. Vilar L , Naves LA , Gadelha MR . Pitfalls in the diagnosis of hyperprolactinemia . Arq  Bras \nEndocrinol Metab . 2003 ; 47 ( 4 ): 347 - 57 \n69. Vilar L , Naves LA . Avaliação diagnóstica da hiperprolactine mia . In: Vilar L , et al ,  editors. \nEndocrinologia Clínica . 5a ed . Rio de Janeiro : Guanabara Koogan ; 2013 . p. 39 - 49 \n70. Huang W , Molitch M . Evaluation and management of galactorrhea . Am Fam Physician .  2012 \n; 85 ( 11 ): 1073 - 80 . \n71. Vilar L  , Czepielewsk MA , Naves  LA , Rollin GA , Casulari  LA , Coelho CE .  Substantial \nshrinkage of adenomas cosecreting growth hormone and prolactin with use of  cabergoline therapy . \nEndocr Pract . 2007 ; 13 ( 4 ): 396 - 402. \n72. Talwar PP. Prevalence of infertility in different population groups in India and its determinants \n1986 in establishing an ART in low resource setting‑page 55. In: Handbook \n73. of Managing Infertility. 1st edn. New Delhi; India: Jaypee Brothers Medical Publishers; 2012 \n74. Unisa S. Childlessness in Andhra Pradesh, India. Reprod Health Matters. 1999;7:54‑64 \n75. Raber W, Nowotny P, Vytiska‑Binstorfer E, Vierhapper H. Thyroxine treatment modified in \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 33 \n \ninfertile women according to thyroxine ‑releasing hormone testing: 5 year  follow‑up of 283 \nwomen referred after exclusion of absolute causes of infertility. Hum Reprod. 2003;18:707‑14 \n76. Trokoudes KM, Skordis N, Picolos MK. Infertility and thyroid disorders. Curr Opin  Obstet \nGynecol. 2006;18(4):446-51. \n77. Davis LB, Lathi RB, Dahan MH. The effect of infertility medic ation on thyroid function  in \nhypothyroid women who conceive. Thyroid. 2007;17:773–7 \n78. Dajan CM, Saravanan P, Bayly G. Whose normal thyroid function is better –yours or  mine? \nLancet. 2002;360:353–4 \n79. Harvard Medical School. Female infertility. 2009 \n80. Macer ML, Taylor HS. Endometriosis and infertility: a review of the pathogenesis and treatment of \nendometriosis-associated infertility. Obstet Gynecol Clin North Am. 2012;39(4):535-549. \ndoi:10.1016/j.ogc.2012.10.002 \n81. Magdy N, El-Bahrawy M. Fallopian tube: Its role in infertility and gynecological oncology. World \nJ Obstet Gynecol. 2014;3(2):35-41. doi:10.5317/wjog.v3.i2.35 \n82. Rebar RW. Problems With the Fallopian Tubes and Abnormalities in the Pelvis . Merck Manual \nConsumer Version. Updated February 2019 \n83. American Society for Reproductive Medicine. Intrauterine Adhesions: What Are They? 2015. \n84. Brigham and Women‟s Hospital. Endometriosis and Fertility. \n85. Shah SM, Towobola OA, Masihleho M.  Diagnosis offallopian tube patency. East  Afr Med J. \n2005Sep;82(9):457-62 \n86. Watson A, Vandekerckhove P, Lilford R, et al. A meta -analysis of the therapeutic role of  oil \nsoluble contrastmedia at hysterosalpingography: a surprising result? FertilSteril 1994; 61:470–77 \n87. Jenkins C, Williams S, Schmidt G. Salpingitis isthimicnodosa: a review of the literature, discussion \nof clinicalsignificance, and consideration of patient management.Fertil Steril 1993; 60:599–607 \n88. De Witt W, Gowrising CJ, Kuik DJ, et al. Onlyhydr osalpinges visible on ultrasound are associated \nwithreduced implantation and pregnancy rates after IVF. HumReprod 1997; 12:170. \n89. Donnez J, Casanas -Roux F. Prognostic factors of fimbrialmicrosurgery. Fertil Steril 1986;  \n46:1089–92. \n90. Young PE, Egan JE, Barlow J, Mulligan WE.Reconstructive surgery for infertility at the  \nBostonHospital for Women. Am J Obstet Gynecol 1970;108:1092–97 \n91. Novy M, Thurmond AS, Patton P, Uchida BT, Rosch J.Diagnosis of cornual obstruction  by \ntranscervical fallopiantube cannulation. Fertil Steril 1988; 50:434–40 \n92. Honore GM, Holden AE, Schenken RS. Pathophysiologyand management of proximal  tubal \nblockage. Fertil Steril1999; 71:785–95 \n93. Thurmond AS, Novy M, Rosch J. Terbutaline in diagnosisof interstitial fallopian tube  obstruction. \nInvest Radiol1988; 23:209–10 \n94. William D. A new hysterographic approach to theevaluation of tubal spasm and spasmolytic \nagents. FertilSteril 1983; 39:105–7 \n95. Winfield AC, Pittaway D, Maxson W, et al. Apparentcornual occlusion in hysterosalpingography: \nreversal byglucagon. Am J Roentgenol 1982; 139:525–27. \n96. Cooper JM, Rigberg HS, Houck R, Aiken M. Incidence,significance, and remission of  tubal spasm \nduring attemptedhysteroscopic tubal sterilization. J Reprod Med 1985;30:39–42 \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 34 \n \n97. Hurd WW, Wyckoff ET, Reynolds DB, et a l. Patientrotation and resolution of unilateral  cornual \nobstructionduring hysterosalpingography. Obstet Gynecol 2003;101:1275–78 \n98. -Bélisle S, Collins JA, Burrows EA, Willan AR. The value of laparoscopy among infertile women \nwith tubal patency. J Soc Obstet Gynaecol Can. 1996;18:326–336 \n99. Ngowa JD, Kasia JM, Georges NT, Nkongo V, Sone C, Fongang E. Comparison of  \nhysterosalpingograms with laparoscopy in the diagnostic of tubal factor of female \ninfertility at the Yaoundé  General Hospital,  Cameroon. Pan Afr  Med J.  2015;22:264–264. doi: \n10.11604/pamj.2015.22.264.8028 \n100. Fayez JA, Mutie G, Schneider PJ. The diagnostic value of hysterosalpingography and \nlaparoscopy in infertility investigation. Int J Fertil. 1988;33:98–101. \n101. Simon A, Laufer N. Unexplained infertility: A reappraisal. Ass Reprod Rev. 1993;3:26– 36 \n102. McDougall AN.   Laparoscopy   in   the   investigation   of   infertility.   Scott   Med   J. \n103. 1976;20:209–216. doi: 10.1177/003693307502000506. \n104. Karande VC, Pratt DE, Rao R, Balin M, Gleicher N. Elevated tubal perfusion pressures  during \nselective salpingography are highly suggestive of tubal endometriosis. Fertil Steril.  1995;64:1070–\n1073. doi: 10.1016/S0015-0282(16)57962-X \n105. Yu X, Cai H, Zheng X, Feng J, Guan J. Tubal restorative surgery for hydrosalpinges in women due \nto in vitro fertilization. Arch Gynecol Obstet. 2018;297:1169 –1173. doi:  10.1007/s00404-018-\n4695-7 \n106. Chan YY, Jayaprakasan K, Tan A, Thornton JG, Coomarasamy A, Raine -Fenning NJ.  \nReproductive outcomes in women with congenital uterine anomalies: a systematic review. \nUltrasound in Obstetrics & Gynecology. 2011; 38: 371-382 \n107. Tomaževič T, Ban-Frangež H, Ribič-Pucelj M, Premru-Sršen T, Verdenik I. Small uterine septum \nis an important risk variable for preterm birth. European Journal of Obstetrics & Gynecology and \nReproductive Biology. 2007; 135: 154-157 \n108. Acién P. Reproductive performance of women with uterine malformations. Human Reproduction. \n1993; 8: 122-126 \n109. Rock JA, Schlaff WD. The obstetric consequences of uterovaginal anomalies. Fertility  and \nSterility. 1985; 43: 681-692. \n110. Rackow BW. Congenital uterine anomalies. Ultrasound Imaging in Reproductive Medicine. 2019; \n12: 121-135 \n111. Lovelace D. Congenital uterine anomalies and uterine rupture. Journal of Midwifery &  Women‟s \nHealth. 2016; 61: 501-506 \n112. Society TAF. The American Fertility Society classifications of adnexal adhesions, distal  tubal \nocclusion, tubal occlusion secondary to tubal ligation, tubal pregnancies, Müllerian  anomalies and \nintrauterine adhesions. Fertility and Sterility. 1988; 49: 944-955 \n113. Troiano RN, McCarthy SM. Mullerian duct anomalies: imaging and clinical  issues.  \nRadiology. 2004; 233: 19-30 \n114. Iverson RE, DeCherney AH, Laufer MR. Clinical manifestations and diagnosis of congenital \nanomalies of the uterus. UpToDate. 2015. (Accessed in April). \n115. Mazouni C, Girard G, Deter R, Haumonte J, Blanc B, Bretelle F. Diagnosis of Müllerian  \nanomalies in adults: evaluation of practice. Fertility and Sterility. 2008; 89: 219-222 \n116. Chan YY, Jayaprakasan K, Zamora J, Thornton JG, Raine -Fenning N, Coomaras amy A.  The \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 35 \n \nprevalence of congenital uterine anomalies in unselected and high-risk populations: a systematic \nreview. Human Reproduction Update. 2011; 17: 761-771 \n117. Marcal, L.; Nothaft, M.A.; Coelho, F.; Volpato, R.; Iyer, R. Mullerian duct anomalies:  MR \nimaging. Abdom. Imaging 2011, 36, 756–764 \n118. Jayaprakasan, K.; Chan, Y.Y.; Sur, S.; Deb, S.; Clewes, J.S.; Raine-Fenning, N.J. Prevalence of \nuterine anomalies and their impact on early pregnancy in women conceiving after assisted \nreproduction treatment. Ultrasound Obstet. Gynecol. 2011, 37, 727–732 \n119. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364(9447):1789–99 \n120. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic  nodules \nof the rectovaginal septum are three different entities. Fertil Steril. 1997;68(4):585–96 \n121. Farland LV, Shah DK, Kvaskoff M, Zondervan K, Missmer SA. Epidemiological and  Clinical \nRisk Factors for Endometriosis. In: D‟Hooghe T, editor. Biomarkers for Endometriosis. Springer \nScience; New York: 2015 \n122. Anaf V, Simon P, El Nakadi I, Fayt I, Simonart T, Buxant F, et al. Hyperalgesia, nerve  infiltration \nand nerve growth factor expression in deep adenomyotic nodules, peritoneal  and ovarian \nendometriosis. Hum Reprod. 2002;17:1895–900 \n123. Wang G, Tokushige N, Markham R, Fraser IS. Rich innervation of deep infiltrating endometriosis. \nHum Reprod. 2009;24:827–34 \n124. Berkley KJ, Rapkin AJ, Papka RE. The pains of endometriosis. Science. 2005;308:1587–9 \n125. Bulun SE. Endometriosis. N Engl J Med. 2009 Jan 15;360(3):268–79. doi: \n10.1056/NEJMra0804690 \n126. Ferguson BR, Bennington JL, Haber SL. Histochemistry of mucosubstances and histology of \nmixed mullerian pelvic lymph node glandular inclusions: evidence for histogenesis by mullerian \nmetaplasia of coelomic epithelium. Obstet Gynecol. 1969;33:617–25 \n127. Sampson JA. Metastatic or embolic endometriosis due to menstrual dissemination of  endometrial \ntissue into the venous circulation. Am J Pathol \n128. Carter JE. Combined hysteroscopic and laparoscopic findings in patients with chronic  pelvic pain. \nJ Am Assoc Gynecol Laparosc. 1994;2:43–47 \n129. Nnoaham KE, Hummelshoj L, Webster P, d'Hooghe T, de Cicco Nardone F, de Cicco  Nardone C, \nJenkinson C, Kennedy SH, Zondervan KT. World Endometriosis Research  Foundation Global \nStudy of Women‟s Health consortium. Impa ct of endometriosis on  quality of life and work \nproductivity: a multicenter study across ten countries. Fertil  Steril. 2011  Aug;96(2):366–373.e8. \ndoi: 10.1016/j.fertnstert.2011.05.090. Epub 2011 Jun \n130. 30. This multi -site study reported that endometriosis is highly debilitating disease which  affects \nsocioeconomic quality and work life of patients. This is one of the articles which  identified the \ndiagnostic delay in women with endometriosis \n131. Greene R, Stratton P, Cleary SD, Ballweg ML, Sinaii N. Diagnostic experience among  4,334 \nwomen reporting surgically diagnosed endometriosis. Fertil Steril. 2009;91:32–9. \n132. Dun EC, Kho KA, Morozov VV, Kearney S, Zurawin JL, Nezhat CH. Endometriosis in  \nadolescents. JSLS. 2015;19(2) doi: 10.4293/JSLS.2015.00019. pii: e2015.00019. \n133. Laufer MR. Current approaches to optimizing the treatment of endometriosis in adolescents. \nGynecol Obstet Invest. 2008;66(Suppl 1):19–27 \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 36 \n \n134. Dierschke DJ, et al. Circhoral oscillations of plasma LH levels in the ovariectomized  rhesus \nmonkey. Endocrinology. 1970;87:850–853 \n135. Clarke IJ, Cummins JT. The temporal relationship between gonadotropin releasing hormone \n(GnRH) and luteinizing hormone (LH) secretion in ovariectomized ewes. Endocrinology. \n1982;111:1737–1739 \n136. Knobil E. The neuroendocrine control of the menstrual cycle. Recent Prog Horm Res. \n137. 1980;36:53–88 \n \n138. Belchetz PE, et al. Hypophysial responses to continuous and intermittent delivery of  \nhypopthalamic gonadotropin-releasing hormone. Science. 1978;202:631–633 \n139. Wetsel WC, et al. Intrinsic pulsatile secretory activity of immortalized luteinizing hormone-\nreleasing hormone-secreting neurons. Proc Natl Acad Sci U S A. 1992;89:4149–4153 \n140. Advis JP, et al. Regulation of gonadotropin releasing hormone release by neuropeptide Y  at the \nmedian eminence during the preovulatory period in ewes. Neuroendocrinology. 2003;77:246–257 \n141. Clomiphene citrate and ovulation induction Vol 4. No 3. 303–310 Reproductive BioMedicine \nOnline; www.rbmonline.com/Article/47 \n142. Fauser BC, Macklon NS. Medical approaches to ovarian stimulatin for infertility. In:  Strauss JF, \nBarbieri RL, editors. Yen and Jaffes Reproductive Endocrinology. 5th edn.  Elsevier Saunders Inc; \npp. 965–1012 \n143. Fauser BC, van Heusden AM. Manipulation of human ovarian function: physiological  concepts \nand clinical consequences. Endocr Rev. 1997;18:71–106 \n144. 139.-van Santbrink EJ, Donderwinkel PF, van Dessel TJ, Fauser BC. Gonadotropin induction  of \novulation using a step -down dose regimen: single -centre clinical experience i n 82 patients. Hum \nReprod. 1995;10:1048–53 \n145. Thurin A, Hausken J, Hillensjo T, et al. Elective single -embryo transfer versus double - embryo \ntransfer in in vitro fertilization. N Engl J Med. 2004;351:2392–2402 \n146. Samir Babayev, M.D.GynecologistReproductive Endocrinologist Rochester,\n MN https://www.mayoclinic.org/diseases-conditions/female-infertility/diagnosis- treatment/drc-\n20354313 \n147. NICE - National Institute for Health and Care Excellence . London: NICE; 2013. \nFertilityproblems:assessment and \ntreatment.https://www.nice.org.uk/guidance/cg156?unlid=86583397720167208641 \n148. ESHRE Capri Workshop Group Intrauterine insemination. Hum Reprod Update. \n149. 2009;15:265–277. doi: 10.1093/humupd/dmp003. \n150. zhao Y, Brezina P, Hsu CC, Garcia J, Brinsden PR, Wallach E. In vitro fertilization: four  decades \nof reflections and promises. Biochim Biophys Acta. 2011 Sep;1810(9):843-52. \n151. Sunderam S, Kissin DM, Crawford SB, Folger SG, Boulet SL, Warner L, Barfield WD.  Assisted \nReproductive Technology Surveillance - United States, 2015. MMWR Surveill  Summ. 2018 Feb \n16;67(3):1-28. \n152. Siristatidis CS, Gibreel A, Basios G, Maheshwari A, Bhattacharya S. Gonadotrophin‐releasing \nhormone agonist protocols for pituitary suppression in assisted  reproduction. Cochrane Database \nof Systematic Reviews 2015, Issue 11. [DOI: 10.1002/14651858.CD006919.pub4] \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 37 \n \n153. Al‐Inany HG, Youssef MAFM, Ab oulghar M, Broekmans FJ, Sterrenburg MD, Smit JG,  et al. \nGonadotrophin‐releasing hormone antagonists for assisted reproductive technology.  Cochrane \nDatabase of Systematic Reviews 2016, Issue 4. [DOI: 10.1002/14651858.CD001750.pub4 \n154. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic  injection \nof single spermatozoon into an oocyte. Lancet 1999;340:17–8. \n155. Benadiva CA, Nulsen J, Siano L, Jennings J, Givargis HB, Maier D. Intracytoplasmic  sperm \ninjection overcomes previous fertilization failure with conventional in vitro fertilization. Fertil \nSteril 1999;72:1041–4 \n156. 150.3. Kastrop PM, Weima SM, Van Kooij RJ, Te Velde ER. Comparison between \nintracytoplasmic sperm injection and in -vitro fertilization (IVF) with high insemination  \nconcentration after total fertilization failure in a previous IVF attempt. Hum Reprod 1999;14:65–9 \n157. 151.. Practice Committee of the American Society for Reproductive Medicine;Practice Committee \nof the Society for Assisted Reproductive Technology. Genetic co nsiderations related to \nintracytoplasmic sperm injection (ICSI).Fertil Steril 2006;86:103–5. \n158. Guzick DS, Overstreet JW, Factor -Litvak P, Brazil CK, Nakajima ST,Coutifaris C, et al.  Sperm \nmorphology, motility, and concentration in fertile and  infertile men.  N Engl  J Med \n2001;345:1388–93. \n159. Tournaye H, Verheyen G, Albano C, Camus M, Van Landuyt L, Devroey P,et al. Intracytoplasmic \nsperm injection versus in vitro fertilization: a randomized controlled  trial and a meta-analysis of \nthe literature. Fertil Steril 2002;78:1030–7. \n160. Van Rumste MM, Evers JL, Farquhar CM. Intra-cytoplasmic sperm injectionversus conventional \ntechniques for oocyte insemination during in vitro fertilisation in patients  with non-male \nsubfertility. Cochrane Database Syst Rev 2003;2:CD001301 \n161. 155.8. Jain T, Gupta RS. Trends in the use of intracytoplasmic sperm injection in theUnited  States. \nN Engl J Med 2007;357:251–7. \n162. American Society for Reproductive Medicine. Intracytoplasmic sperm injection (ICSI).  Fertil \nSteril 2008;90:S187 \n163. American Society for Reproductive Medicine. (2012). Third-party reproduction (sperm, egg, and \nembryo donation and surrogacy): A guide for patients. Retrieved May 31, 2016, \n164. Sherman JK, Bunge RG. Effect of glycerol and freezing on some staining reactions of human \nspermatozoa. Proc Soc Exp Biol Med. 1953;84:179–80. \n165. Critser JK. Current status for semen banking in the USA. Hum Reprod. 1998;13:55–67. \n \n166. Botchan A, Hauser R, Gamzu R, Yogev L, Paz G, et al. Results of 6139 artificial \ninsemination cycles with donor spermatozoa. Hum Reprod. 2001;16:2298–304 \n167. We care health services article egg donation in india The procedure of Egg Donation in India \nhttps://wecareindia.com/egg-donation-in-india/ \n168. Shenfield F, Pennings G, Cohen J, Devroey P, de Wert G, Tarlatzis B. ESHRE Task Force on \nethics and law 10: Surrogacy. Hum Reprod. 2005;20:2705–7 \n169. Maheshwari A, Griffiths S, Bhattacharya S. Global variations in the uptake of single embryo \ntransfer. Hum Reprod Update. 2011;17:107–20 \n170. Jadva V, Murray C, Lycett E, MacCallum F, Golombok S. Surrogacy: The experiences of \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 38 \n \nsurrogate mothers. Hum Reprod. 2003;18:2196–204 \n171. AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE • 1209 Montgomery \n172. Highway • Birmingham, Alabama 35216-2809 \n173. Dural O, Yasa C, Keyif B, Celiksoy H, Demiral I, Ozgor BY. Effect of infertility on quality of life \nof women: a validation study of the Turkish FertiQoL. Jhuman Fertility. 2016;19(3):186–91. \n174. Cousineau TM, Domar AD. Psychological impact of infertility. Best Pract Res Clin  Obstet \nGynecol. 2007;21(2):293308. \n175. Kamel Remah M. Management of the infertile couple: an evidence -based protocol. J  Reprod Biol \nEndocrinol. 2010;8(1):301–6. \n176. van Balen F, Bos HM. The social and cultural consequences of being childless in poor - resource \nareas. Facts Views Vis Obgyn. 2009;1(2):106–21. \n177. Obi SN, Onah HE, Okafor II. Depression among Nigerian women following pregnancy  loss. Int J \nGynecol Obstet. 2009;105(1):602 \n178. Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive  \ntechnologies and global movements in the 21st century. Jhum Reprod Update. 2015;21(4):411–26. \n179. Farrokh Eslamlou HR, Haji Shafiha M, et al. The effect of primary infertility on the  quality of life \nof women of Oroumieh, Iran. Oroumieh Med J. 2014;25(598):604–7 \n180. Maroufizadeh S, Karimi E, Vesali S,  Omani SR. Anxiety and depression after failure of  assisted \nreproductive treatment among patients experiencing infertility. Int J Gynaecol  Obstet. \n2015;130(3):253–6. \n181. Shoham Z, Zosmer A, Insler V. Early miscarriage and fetal malformations after induction of \novulation (by clomiphene citrate and/or human menotropins), in vitro fertilization, and gamete \nintrafallopian transfer. Fertil Steril 1991; 55: 1–11. \n182. 175.2. Hull MGR, Glazener CMA, Kelly NJ et al. Population study of causes, treatment and  \noutcome of infertility. Br Med J 1985; 291: 1693–7. \n183. Greenblatt RB, Barfield WE, Jungck EC, Ray AW. Induction of ovulation with MRL-41. \n184. JAMA 1961;178: 101. \n185. Greenblatt RB, Roy S, Mahesh VB, Barfield W, Jungck EC. Induction of ovulation. Am J Obstet \nGynecol 1962; 84: 900–7. \n186. Karow WG, Payne SA. Pregnancy after clomiphene citrate treatment. Fertil Steril 1968; 19: 351–\n62 \n187. MacGregor AH, Johnson JE, Bunde CA. Further clinical experience with clomiphene citrate. \nFertil Steril 1968; 19: 616–22. \n188. Adashi EY, Rock JA, Sapp KC et al. Gestational outcome of clomiphene-related conceptions. \nFertil Steril 1979; 31: 620–6 \n189. Garcia J, Jones GS, Wentz AC. The use of clomiphene citrate. Fertil Steril 1977; 28: 707–17. \n190. Kurachi K, Aono T, Minagawa J, Miyake A. Congenital malformations of newborn infants \nafter clomiphene-induced ovulation. Fertil Steril 1983; 40: 187–9. \n191. Kousta E, White DM, Franks S. Modern use of clomiphene citrate in induction of ovulation. \nHum Reprod Update 1997; 3: 359–65 \n192. Boue JG, Boue A. Increased frequency of chromosomal anomalies in abortions after induced \novulation. Lancet 1973; i: 679. \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 39 \n \n193. Dyson JL, Kohler HG. Anencephaly and ovulation stimulation. Lancet 1973; i: 1256 –7. 186.Harlap \nS. Ovulation induction and congenital malformations. Lancet 1976; ii: 961. \n194. Cornel MC, Kate LPT, Dukes MN et al. Ovulation induction and neural tube defects. \n195. Lancet 1989; i: 1386. \n196. Mills JL,  Simpson JL,  Rhoads GG  et al.  Risk of neural  tube defects  in relation  to maternal \nfertility and fertility drug use. Lancet 1990; 336: 103–4 \n197. Lunenfeld B, Serr DM, Mashiach S et al. Therapy with gonadotropins: where are we  today? \nAnalysis of  2890 menotropin treatment cycles in 914 patients. In:  Insler V, Bettendorf G, eds. \nAdvances in diagnosis and treatment of infertility. Amsterdam: Elsevier, 1981: 27–31. \n198. Ben-Rafael Z, Dor J, Mashiach S et al. Abortion rate in pregnancies following ovulation  induced \nby human menopausal gonadotropin/human chorionic gonadotropin. Fertil Steril 1983; 39: 157 \n199. Miyake A, Kurachi H, Wakimoto H et al. Second pregnancy with spontaneous ovulation following \nclomiphene- or gonadotropin-induced pregnancy. Eur J Obstet Gynecol Reprod Biol 1988;27: 1–5. \n200. Corsan GH & Kemmann E. Risk of a second consecutive first -trimester spontaneous abortion in \nwomen who conceive with menotropins. Fertil Steril 1990; 53: 817–21. \n201. Balen AH, Braat DDM, West C, Patel A, Jacobs HS. Cumulative conception and live  birth rates \nafter the treatment of anovulatory infertility. An analysis of the safety and  efficacy of ovulation \ninduction in 200 patients. Hum Reprod 1994; 9: 1563–70. \n202. Homburg R, Eshel A, Armar NA et al. One hundred pregnancies after treatment with  pulsatile \nluteinising hormone-releasing hormone to induce ovulation. BMJ 1989; 298: 809–12. \n203. Nillius SJ, Wilde L. Effects of prolonged luteinising hormone-releasing hormone therapy on  \nfollicular maturation, ovulation and corpus luteum function in amenorrheic  women with anorexia \nnervosa. Uppsala J Med Sci 1978; 84: 21–35. \n204. Braat DDM, Schoemaker R, Schoemaker J. Life table analysis of fecundity in intravenously \ntreated gonadotropin-releasing hormone treated patients with normogonadotropic and \nhypogonadotropic amenorrhea. Fertil Steril 1991; 55: 266–71. \n205. Van der Spuy ZM, Steer PJ, McCusker M, Steele SJ, Jacobs HS. Pregnancy outcome in  \nunderweight women following spontaneous and induced ovulation. BMJ 1988; 296: 962–5. \n206. Armar NA, McGarrigle HHG, Honour JW et al. Laparoscopic ovarian diathermy in the  \nmanagement of anovulatory infertility in women with polycystic ovaries: endocrine changes and \nclinical outcome. Fertil Steril 1990; 53: 45–9 \n207. Out HJ, Coelingh Bennink HJ. Clomiphene citrate or gonadotrophins for induction of  ovulation?. \nHum Reprod 1998; 13: 2358–61 \n208. de Ruiter A, Mercey D, Anderson J, et al. British HIV Association and Children‟s HIV  \nAssociation guidelines for the management of HIV infection in pregnant women 2008.  HIV Med \n2008; 9: 452–502. \n209. Frodsham LCG BF, Barton S, Gilling-Smith C. Human immunodefi ciency virus infection and \nfertility care in the United Kingdom – demand and supply. Fertil Steril 2006; 85: 285–9. \n210. Coll O, Lopez M, Vidal R, et al. Fertility assessment in non -infertile HIV -infected women and \ntheir partners. Reprod Biomed Online 2007; 14: 488–94. \n211. Coll O, Fiore S, Floridia M, et al. Pregnancy and HIV infection: A European consens us on \nmanagement. AIDS 2002; 16(Suppl 2): S1–S18. \n\n \nInternational Journal for Multidisciplinary Research (IJFMR) \n \nE-ISSN: 2582-2160   ●   Website: www.ijfmr.com    ●   Email: editor@ijfmr.com \n \nIJFMR22061060 Volume 4, Issue 6, November-December 2022 40 \n \n212. Coll O, Lopez M, Hernandez S. Fertility choices and management for HIV -positive women. Currt \nOpin HIV AIDS 2008; 3: 186–92. \n213. Martinet V, Manigart Y, Rozenberg S, et al. Ovarian response to stimulation of HIV- positive \npatients during IVF treatment: a matched, controlled study. Hum Reprod 2006; 21: 1212–17 \n214. Coll O, Suy A, Figueras F, et al. Decreased pregnancy rate after in -vitro fertilization in  HIV-\ninfected women receiving HAART. AIDS 2006; 20: 121–3 \n215. Brunham RC, Cheang M, McMaster J, Garnett G, Anderson R. Chlamydia trachomatis,  infertility, \nand population growth in sub-Saharan Africa. Sex Transm Dis 1993; 20: 168– 73. \n216. Brunham RC, Garnett GP, Swinton J, Anderson RM. Gonococcal infection and human  fertility in \nsub-Saharan Africa. Proc Biol Sci 1991; 246: 173–7. \n217. Frodsham LCG, Cox AD, Almeida PA, Rozis G, Gilling -Smith C. In vitro fertilisation in  HIV \npositive women: risk of mother to embryo viral transmission. Hum Reprod 2004; 9(Suppl 1): 138 \n218. Gilling-Smith C, Almeida P. HIV, hepatitis B and hepatitis C and infertility: reducing  risk. Hum \nFertil (Camb) 2003; 6: 106–12.. \n219. Lutgens SP, Nelissen EC, van Loo IH, et al. To do or not to do: IVF and ICSI in chronic  hepatitis \nB virus carriers. Hum Reprod 2009; 24: 2676–8 \n220. MacDonald M, Crofts N, Kaldor J. Transmission of hepatitis C virus: rates, routes, and  cofactors. \nEpidemiol Rev 1996; 18: 137–48. \n221. Pasquier C, Daudin M, Righi L, et al. Sperm washing and virus nucleic acid detection to  reduce \nHIV and hepatitis C viru s transmission in serodiscordant couples wishing to have  children. AIDS \n2000;14: 2093–9 \n222. Halfon P, Giorgetti C, Bourliere M, et al. Medically assisted procreation and transmission of \nhepatitis C virus: absence of HCV RNA in purifi ed sperm fraction in  HIV co-infected patients. \nAIDS 2006; 20: 241–6","source_license":"CC0","license_restricted":false}