{"paper_id":"ad1e825d-721d-4ef9-8032-acdeb9b69218","body_text":"Infertility, which is defined as being unable to conceive\nafter having unprotected sex for more than one year, affects approximately 20% of couples worldwide and 25%\nof couples in developing countries. It affects diverse aspects of infertile couples’ lives (mental, physical, sexual,\nand social aspects) and thus requires appropriate interventions ( 1 ,  2 ). Accordingly, understanding the main cause of\ninfertility and choosing the right treatment method within\nthe patient's affordability and availability is very important for designing treatment methods and programs ( 2 ,  3 ).\nAssisted reproductive technologies (ART) are usually used as strategies to manage\ninfertility with multifactorial causes (including genetically predisposed diseases). ART has\nevolved rapidly since 1976, and scientists have been trying to establish the proper approach\noption for each infertile couple. Among assisted reproductive technologies,  in\nvitro  fertilization (IVF) is the most popular ( 4 ).\nIVF is a multi-step procedure meant to help conception or\ncounteract genetic issues. In the first step of IVF, mature eggs\nare obtained from ovaries. These are fertilized by sperm in the laboratory. The next step is transference of the fertilized\negg (embryo) to the uterus. In general, the full IVF course\nrequires about three weeks depending on stimulation protocols, and sometimes these levels are divided into different\nsublevels, and the process may take more time ( 5 ).\nDespite continuous advances in IVF and increasing success, only about one-third of women undergoing IVF will\nbecome pregnant, and about 60% of cases fail ( 6 ). Various\nfactors are considered as causes of infertility, such as infertility duration, lifestyle, recovered eggs, endometrial thickness, number of transferred embryos, and quality of blastocyst, as well as demographic factors, like ethnicity ( 7 ).\nThe efficacy of IVF depends on the treating clinic’s\noverall success rate and the infertile couple’s characteristics. Accordingly, among the factors thought to affect\nIVF success rate are the physical environment, genetics,\npsychological factors, serum levels of some hormones,\nsperm and egg characteristics, as well as age and body\nmass index (BMI) of couples ( 8 - 10 ).\nThe objective of this review is to investigate the factors that affect IVF failure and success rates.\nThis review is focused on studies of multiple factors\nand their influence on the outcome of IVF technology.\nArticles were eligible if they evaluated the association\nbetween any factor and IVF outcome. Articles were\nselected if the target population consisted of patients\nundergoing IVF and intra-cytoplasmic sperm injection\n(ICSI) procedures.\nA thorough search of four databases (PubMed, Embase,\nCinahl, and Cochrane) was conducted from their inception\nuntil March 2021. The reference lists of review articles and\nrelevant studies were hand-searched to identify other potentially eligible studies. Abstracts from conference proceedings were also considered. No language filters or any other\nrestrictions were applied. Keywords used for the searchers\nwere: IVF, age, BMI, psychological factors, sperm features,\novarian stimulation, hormonal profile, ICSI, IVF, single-nucleotide polymorphism (SNP), and genetic. We downloaded\nall references identified into EndNote software (version X7).\nTwo authors (Radin Dabbagh Rezaeiyeh, and Arian Mehrara) agreed on the inclusion criteria. Articles were incorporated if they were: original, review, or peer-reviewed research. One author (Amin Mohammad Ali Pour) conducted\nthe initial screening analysis. After removing duplicates and\nscreening the titles and abstracts of the articles, those meeting the inclusion criteria were reviewed. The reference list of\nevery selected article was carefully checked to identify other\npotentially eligible studies.\nOur search resulted in 1278 articles (excluding duplicates).\nThe article selection process was such that articles that did not\nqualify and did not meet the inclusion criteria were removed\nat the title screening. Three hundred twenty-one articles met\ninclusion criteria and were chosen for abstract screening. Out\nof those 321 articles, 180 were found eligible for full text\nscreening. After assessing the full text of these 180 papers,\nwe selected 70 articles for further reading ( Fig .1 ).\nIn Table 1, we present a summary of factors that affect\nthe failure and success of IVF. Each factor is explained\nand discussed at the end of the Table.\nSummary of the factors that have been identified as influencing IVF outcomes and their effects on fertility\nBMI; Body mass index, LH; Luteinizing hormone, FSH; Follicle-stimulating hormone, AMH;\nAnti-müllerian hormone, PGD; Preimplantation genetic testing, ART; Assisted\nreproductive technology, and IVF;  In vitro  fertilization.\nInitial to final search steps for selecting manuscripts.\nWomen's age is considered among the most important\nelements affecting the likelihood of achieving pregnancy\nin ART programs. As age increases, women’s fertility and\nlive birth rates decrease significantly (especially after\n35 years). Increasing maternal age leads to a decrease in\npregnancy rate (although this is similar between IVF and\nICSI), fertilization rate, and number of recovered eggs\n( 11 ,  12 ). Accordingly, decreased female reproductive capacity increases with age due to the gradual reduction of\neggs from the ovaries and a significant reduction in egg\nquality. Morphological evaluation methods for human\nembryos have proven that maternal age has a significant\neffect on the quality of human embryos. In addition, the\nrate of aneuploidy in human embryos increases with age\n( 13 ,  14 ).\nThe results of the study by Yan et al. ( 15 ) showed that\nolder women had a weaker response during controlled\novarian hyper-stimulation (COH), fewer retrieved eggs,\nlow oocyte fertilization rate, low-quality embryo rates,\nlow embryo implantation rate, low delivery, high abortion, and high preterm delivery. Goldman et al. ( 16 ) stated\nthat age-related fertility decline had much more effect on\nthe live birth rate at older ages than BMI. As age can’t be\naltered, it can be concluded that spending more time on\nlowering BMI before IVF is of significant benefit in older\nwomen.\nIn addition to age, the obesity factor is also very important in reproductive support programs. The harmful\nconsequences of obesity on the reproductive system include maternal complications, infertility, and menstrual\ndisorders. Decreased fertility is attributed to various parameters in obese women, such as endocrine and metabolic dysfunctions, which sequentially may affect follicular proliferation, implantation, and the growth of clinical\npregnancy ( 17 ). Hence, monitoring the effects of body\nweight during IVF is of paramount importance. Many\nstudies have demonstrated that pregnancies and live birth\nrates in overweight and obese individuals are reduced in\ncomparison to women of normal weight ( 18 ,  19 ). Possible causes of these discrepancies include increased gonadotropin requirements during ovarian stimulation, fewer\nrecovered oocytes, decreased serum estradiol concentrations, and low fertilization rates. In contrast, other studies\nhave shown that obesity has no effect on gonadotropin\nrequirement, and the number of ovarian stimulation days\ndoes not affect estradiol levels ( 20 ,  21 ).\nIt has been found that obese women who become pregnant after IVF are at risk of miscarriage and obstetric difficulties generally. But it must be taken into consideration that whether achieving a specific BMI and spending a lot\nof time losing weight before the beginning of the IVF cycle is detrimental to the possibility of live birth, given that\nthe woman is constantly ageing. Obesity increases ovulation induction time, decrease edtradiol peak, and decrease\nthe number of mature follicles. In addition, obesity may\nadversely affect the quality of eggs and embryos ( 22 ,  23 ).\nDokras et al. ( 22 ) observed approximately 1,300 patients in one study, the IVF failure\nrate was 25% in obese women in comparison to 10.9% in normal weight women. In addition,\nIVF failure in obese women with polycystic ovary syndrome (PCOS) is more probable than in\nnormal women. Contrary to these findings, many studies, including the study by Kim et al.\n( 24 ), did not find any considerable gap in clinical pregnancy rates between obese and\nnormal weight women. In a recent study Maged et al. ( 25 ) found that implantation, chemical\npregnancy, and clinical pregnancy rates were inversely related to increasing BMI. From\nJanuary 2013 to February 2018, Hallisey et al. ( 26 ) performed a cohort study. Their\npopulation included women aged over 45 years who underwent IVF with PGT (preimplantation\ngenetic testing). Five hundred thirtythree cycles were separated into 3 groups of women\ncategorized by BMI as normal, overweight, and obese. Euploidy rate was the primary\noutcome. Their study showed that a higher miscarriage possibility in women with higher BMI\nand a lower probability of having a live baby after IVF. They stated that the root cause\nof these discrepancies is currently unknown and it is accepted that obesity may be\nassociated with higher rates of aneuploidy, which can lead to worsening pregnancy\noutcomes. The dosage of gonadotrophin required for ovarian stimulation is higher in women\nwith BMI more than 25 kg/m 2  is also but not the ovarian stimulation duration\n( 27 ).\nDespite the prevalence of infertility, most infertile\nwomen do not share their stories with family or friends,\nthus increasing their psychological vulnerability. Inability\nto reproduce normally can result in low self-esteem and\nfeelings of shame and guilt. These negative emotions can\nlead to different levels of depression, nervousness, distress, and poor quality of life. Most women undergoing\nART are frequently anxious and depressed due to infertility. Nearly 32% of women in the early stages of infertility\ntreatment are at risk of mental disorders ( 28 - 30 ). Several\nstudies have examined the relationship between psychological symptoms before and during the ART cycle and\nsubsequent pregnancy. These have provided conflicting results. Some have shown that the pregnancy rate is\nlower among distressed women before and during treatment, while other studies have not found such a result\n( 31 ). Several plausible psychological pathways play a\nrole in the likelihood that a woman's distress will affect\nher fertility or may disrupt infertility treatment success.\nThese pathways include the hypothalamic-pituitary adrenal (HPA) axis, which plays a role in stress response\nregulation, and the hypothalamic-pituitary gonadal axis (HPG), which regulates reproduction ( 32 ). The physiological pathways that influence psychological factors\ninvolved in pregnancy are still generally unknown, but\nthese factors can be associated with incomplete ovulation,\nsecondary amenorrhea, and irregular menstrual periods.\nVarious mechanisms have been proposed for the negative\neffect of psychological factors on infertility, including\nimpaired gonadotropin secretion, local effect of catecholamine on the uterus and fallopian tubes, and impaired\nimmune processes involved in maintaining fertility ( 33 ).\nCesta et al. ( 34 ) studied women who received infertility\ntreatment from September 2011 to December 2013 and\nfollowed them until December 2014. Before IVF initiation, data was gathered through an online questionnaire\nas well as clinical charts. Cortisol from saliva samples\nwas measured and the correlation between stress and cycle outcomes (embryo and oocyte quality parameters and\nclinical pregnancy) was examined. Unexpectedly, it was\nrevealed that women with higher salivary cortisol concentration had no different IVF outcome than women with\nnormal cortisol levels. Psychosocial care could be helpful for couples experiencing infertility treatment. It has\nbeen established that psychosocial care can be effective\nin decreasing plasma cortisol levels and psychological\ndistress and can improve the clinical rate of pregnancy\nsignificantly. Another study by Cui et al. ( 35 ) showed that\ndepression during IVF has adverse effects on pregnancy\noutcomes. Accordingly, measurement of angiotensin II\nand salivary amylase may be a reference indicator for patients' psychological status during IVF.\nSimultaneous combined endocrine events involving the\nanterior pituitary, hypothalamus, and ovaries are a reflection of the menstrual cycle. These events are important\nfor successful ovulation, egg growth, implantation, and\nfertilization. In general, the levels of follicle-stimulating\nhormone, estradiol, luteinizing hormone, and anti-mullerian hormone affect the success or failure of IVF, so it\nis necessary to check these hormones before performing\nany ART. Gonadotrophins [follicle-stimulating hormone\n(FSH) and luteinizing hormone (LH)] are used for ovulation during IVF procedure ( 36 ). The functions of some of\nthese hormones are listed below:\nFSH helps in regulating the menstrual cycle and producing eggs. On day 2 or 3 of the menstrual cycle, FSH\nlevels are tested to determine ovarian function and assess\negg quality. Generally, women with high levels of blood\nFSH on day 2 or 3 of the menstrual cycle have a smaller\nchance of having a live baby than other women of the\nsame age, even with ovulation induction and IVF ( 37 ).\nAbdalla and Thum ( 38 ) studied all patients who were candidates for IVF/ICSI treatment between January 1997 and\nDecember 2001 in Lister hospital, London. Patients were\ndivided into four groups by FSH level. Follicle maturity,\nmiscarriage rate, pregnancy rate, live birth rate, were defined as outcome measures. The authors concluded that\nan increase in basal FSH levels did not indicate a deterioration in egg and embryo quality and did not lead to\na decrease in fertilization or an increase in abortion. The\nfindings of this study showed that the decrease in pregnancy rate is due to the reduction in the number of eggs\ncollected and consequently the limited selection of available embryos for transfer.\nBesides the quantification of FSH, ovarian function\nand egg condition can be evaluated by measuring estradiol (an important form of estrogen). Estradiol is also\nexamined on day 2 or 3 of the menstrual cycle. These\ntest results are not definite indicators of infertility,\nbut increased abnormal levels are associated with decreased response to ovulation-inducing drugs resulting\nin reduced IVF success. The human corpus luteum (CL)\nproduces significant amounts of progesterone (P4), estradiol (E2), androgens, growth factors, and nonsteroidal hormones. The overall maintenance of CL function\ndepends entirely on the regular stimulation of pituitary\nluteinizing hormone (LH) or human placental gonadotropin (hCG) to maintain steroidogenesis in granulosa\ncells ( 39 ). Drakakis et al. ( 40 ) assessed the effect of estradiol support on IVF success. They performed their\nprospective study in the assisted reproduction unit of the\nFirst Department of Obstetrics and Gynecology of the\nAthens University Medical School, from August 2004\nto February 2005. They examined patients who were\nunder IVF/ICSI treatment. Implantation and pregnancy\nrates assessed in the two groups were considered as major outcome measures. They found a steep elevation in\nimplantation rate and pregnancy rate in women who received luteal phase estradiol support compared to women who did not. However, the mean number of fertilized\noocytes, transferred embryos, and retrieved oocytes approximately remained the same.\nLH stimulates the ovaries to release eggs and begin to\nproduce progesterone (a hormone that prepares the uterine environment for the fertilized egg to grow). LH can be\ndetected in a woman’s urine just before ovulation. Urine\nLH tests are frequently conducted to help with the timing\nof intercourse to raise the chance of pregnancy ( 41 ).\nAbbara et al. ( 42 ) showed that there was an unexpected\nnegative association between increased progesterone and\nLH levels during egg maturation. In addition, elevated\nprogesterone appears to be the most reliable biochemical\npredictor of oocyte maturation following all stimulation\nfactors.\nRight after ovulation, the ovaries produce progesterone. Progesterone prepares the uterus\nfor the arrival of a fertilized egg approximately in the middle of the cycle - 12 to 16\ndays after the first day of the menstrual cycle. Progesterone concentration generally\npeaks within 7 days of ovulation, and the amount of blood progesterone can be measured\nthrough blood tests. When a basal level of blood progesterone is established, the doctor\nwill order a mid-luteal serum progesterone test around day 21 of the menstrual cycle ( 43 ).\nTulic et al. ( 44 ) at the Gynecology and Obstetrics Clinic Center of Serbia conducted a\ncohort study. The study included all patients who met the criteria of inclusion\n(infertility diagnosed,  18 -40 years, regular menstrual cycle,  18 -30 kg/m 2  BMI,\n 18 -40 years, without a legal guardian), enrolled in the ART procedure during the study\nperiod (January 2015 to December 2015). Embryos were classified into four classes: class A\n(perfect symmetry), class B (moderate asymmetry), class C (pronounced asymmetry). Main\noutcome measures included pregnancy outcome and procedure success. They stated that low\nlevels of progesterone on oocyte retrieval day (<2.0 ng) in an ART procedure is\nassociated with high levels of FSH and low levels of AMH and lead to the delivery of\nhealthy infants in more than 50% of cases. However, many researchers have found no\nsignificant difference between high levels of progesterone and a reduced pregnancy rate\ndue to different data assessment protocols ( 45 ).\nAMH is a glycoprotein and known as a member of the\ngrowth factors of the β family. This hormone is produced\nby the antral and small antral follicles in the ovary and\nplays a significant part in folliculogenesis and determining the number of primary follicles. In addition, AMH\nlevels shows a good correlation with ART outcomes and\nare thus considered as the most accurate biomarkers for\novarian storage ( 46 ). In general, current ovarian stimulation protocols are performed during IVF treatments\nto personalize protocols based on female AMH levels\n( 47 ). Although there is no definitive value for normal\nand abnormal AMH, it is generally accepted that AMH\n>0.8-1.0 ng/ml indicates normal ovarian reserve ( 48 ).\nIt is well accepted that young women with high AMH\nlevels have significant fertility performance, while older\nwomen with low AMH levels have poor IVF outcomes.\nHowever, due to high individual heterogeneity, there are\ndifferences in some patients ( 49 ). Güngör and Gürbüz\n( 50 ) carried out a retrospective study between November 2014 and September 2019 at the Gynecology and\nIVF Department. They chose a logistic regression model\nrather than linear regression and negative binomial regression due to better dataset fit. Patients were separated\ninto three groups (15 oocytes or more=excessive ovarian\nresponse, 6 to 15 oocytes=normal ovarian response, and\n5 oocytes or less=weak ovarian response). They considered the number and the quality of the retrieved oocytes\nas a means of ovarian response quality. They found that\nhigher levels of serum AMH is associated with higher\nquality of ovarian response (especially the number and\nquality of eggs).\nIn the study of infertile couples, sperm testing is the\nmost important and basic method to assess the cause of\ninfertility and choose the treatment method. Evaluation\nof sperm characteristics such as motility, total number,\nand morphological abnormalities of sperm seems to be\nvery important to predict successful fertilization, implantation, fetal growth, and continuous pregnancy. Various studies have been performed on the role of different\nsemen parameters on fertilization and pregnancies after\nIVF. Higher sperm motility and sperm total number are\nassociated with higher chance of pregnancy and fertilization ( 51 ).\nSperm morphology is one of the most important parameters. Sperm deformity is a reliable predictor of fertility\nsuccess in patients undergoing IVF ( 52 ). According to\nthis criterion, when less than 14% of sperm are of normal\nmorphology the pregnancy rate decreases. In cases where\nnormal morphology is less than 4%, the treatment result\nmay be very poor ( 53 ).\nAnother parameter that has been investigated for its\neffect on reproductive fertility techniques is the age of\nmen. Older age is significantly associated with decreased\nsemen volume, sperm count, motility, and normal morphology ( 54 ). Male genital infection is one of the leading\ncauses of male infertility worldwide. Bacterial invasion\nof the reproductive system has often been shown to be\nassociated with decreased sperm function and lead to infertility ( 55 ). The quality of semen is so important for the\nIVF outcome and nutrients are among the most important\nfactors, affecting the quality of semen ( 56 ).\nSilea et al. ( 54 ) examined 500 semen samples from\nof patients who sought infertility treatment over 5 years\n(April 2013-April 2017). They evaluated semen samples\nboth macroscopically and microscopically using WHO\ncriteria published in 2010 as the standard threshold. Their\nfindings showed that sperm volume and pH were not affected by age but that sperm viability and progressive\nmotility decrease with age. According to the results of\nthe study by Morin et al. ( 57 ), total motile sperm count\n(TMSC) is the most significant of all the parameters used\nto assess sperm quality. In addition, this study, along with\nother studies, has shown that TMSC counts are superior\nto WHO criteria in predicting the success of IVF cycles.\nThere is a significant difference between the samples of\nsemen contaminated with bacteria compared to the control group in terms of reduced sperm concentration and a\nsignificant reduction in sperm motility ( 55 ).\nIn recent years, seemingly ineffective genetic differences, known as genetic polymorphisms among healthy people in the community, have been the focus of studies in\nmany multifactorial diseases, including miscarriage and\nimplant failure. In general, the genetic analyses involved\nin ART are based on methods of pre-implantation genetic diagnosis (PGD) and analysis of genetic variants affecting\nthe success or failure of IVF.\nSince IVF technology has emerged, multiple attempts\nhave been made to increase efficiency and success. Accordingly, selecting a healthy fetus is considered one of\nthe most important strategies, every aspect of which has\nbeen evaluated. Staessen et al. ( 58 ) reported that in women over the age of 37, just 35% of day 3 embryos with\nover eight cells and 65% of proliferating blastocysts were\nnormal. PGD methods are designed to minimize the possibility of transmitting genetically abnormal embryos after\nIVF. Theoretically, choosing genetically normal embryos\nfor transmission leads to more successful pregnancies and\nfewer miscarriages ( 59 ). Genetic techniques used to select\ngenetically normal embryos include fluorescence in situ\nhybridization (FISH), comparative genomic hybridization (CGH), whole genome amplification (WGA), array-CGH, next-generation sequencing, real-time quantitative\npolymerase chain reaction (RT-qPCR), and SNP arrays.\nSo far, several studies have been performed on the effects of different SNPs on various\naspects of human reproduction, including recurrent miscarriage, infertility, and fetal\nimplant failure. The association of SNPs in various genes, including\n MTHFR , Leiden factor V, progesterone receptor, FSH receptor,\nplasminogen activating factor ( PAI-1 ), prothrombin, and estrogen receptor\ngene, with different aspects of fertility has been observed.\nSeveral studies show that thrombophilia leads to repeated implantation failure. Leiden factor V genetic mutations\nand prothrombin G20210A mutations have generally been\nshown to lead to failure of ART ( 60 ).\nThe  P53  gene is considered to be one of the genes most integral to the\nefficient regulation of different physiological processes, including fertility. This gene\ninteracts with the  LIF-1  gene and plays a crucial role in controlling and\nregulating the implantation process. LIF levels are seriously reduced in most females with\ninfertility of unknown cause. Some studies suggest that the prevalence of the codon 72\npolymorphism in the  P53  gene has a significant effect on implantation\nrejection rate in IVF cycles ( 61 ).\nGrowing evidence suggests that vitamin B status may modulate infertility treatment\noutcomes. Water-soluble B vitamin folate is believed to be vital for biosynthetic and\nepigenetic processes and furthermore, regulate the synthesis and methylation of nucleic\nacids and proteins. As a result, folate has been proven to be essential during follicular\nand embryonic developmental periods ( 62 ). The  MTHFR  gene is one of the\nkey genes in the folate pathway. The  MTHFR : c.677C>T polymorphism results\nin a significant change in folate concentration. Because enzyme activity and serum folate\nconcentrations are highest in people with CC wild genotype, this is considered to be the\nmost effective genotype for health. However, current discoveries suggest that, according\nto the IVF treatment outcome, the heterozygous CT genotype of  MTHFR  in\nnucleotide 677 of the mother results in a higher percentage of good quality embryos and a\nmajor chance of clinical pregnancy compared to the homozygous CC and TT genotypes.\nConsistent with these outcomes, it has been shown that the CT genotype, instead of the CC\ngenotype in the woman significantly increases the chances of getting pregnant with IVF\ntreatment ( 63 ). Another polymorphism studied is the  MTHFR : c.1298A>C,\nwhich is associated with higher concentrations of basal FSH and a reduced reaction to\novarian stimulation. The study by Rosen et al. showed that the CC genotype reduced the\novarian response to FSH stimulation compared to the AA and AC genotypes ( 64 ).\nThe solute-carrier gene (SLC) superfamily encodes membrane-bound transporters. A\nprospective study by Haggarty et al. ( 63 ) carried out from October 2000 to September 2004\nincluded 602 women undergoing fertility treatment. Plasma and red-blood-cell\nconcentrations were measured by radioimmunoassay and the absorbed amount of vitamin B12\nand folate were evaluated through a questionnaire. Five B-vitamin-associated-gene variants\nwere measured in women who were treated, as well as 932 women who conceived naturally.\nThey found that the  SLC19A1  c.80G>A polymorphism increased homocysteine\n(Hcy) concentration in heterozygous GA people compared to patients with wild-type\ngenotype. Higher concentrations of Hcy usually lead to detrimental effects on IVF\noutcomes.\nIn addition, other variants involved in the success rate of IVF include MTHFR: c.677C>T\nand CTH (cystathionine gamma-lyase) c.1208G>T. Accordingly, heterozygous individuals have\nfavorable IVF results for these variants compared to wild-type homozygous individuals\n( 65 ).\nThe  LHB  gene (Luteinizing hormone beta) is located in the 11p13\nchromosome region and has three exons. Trp8Arg, Ile15Thr, and Gly102Ser polymorphisms lead\nto menstrual irregularities, infertility, and recurrent miscarriages. Furthermore, in\nwomen undergoing IVF treatment, these variants have been shown to play a marked role in\nthe IVF success rate ( 66 ).\nGrowth differentiation factor 9 ( GDF9 ) and bone morphogenetic protein 15\n(BMP15) gene are expressed in oocytes from primary phase follicles. Both proteins play a\nkey role in specifying follicle growth and ovulation rate. Accordingly, polymorphisms in\nthese genes ( GDF9 : c.546G>A,  BMP15 : c.2673C>T, c.29C>G,\nIVS1+905A>G) are also associated with fertility success rates and increased occurrence of\ndizygotic twins ( 67 ).\nOne of the important genes in the pathway of ovarian metabolism is the aromatase gene\n( CYP19A1 ). Aromatase is viewed as one of the main enzymes in ovarian\nsteroidogenesis, which catalyzes the ultimate stage of conversion of testosterone and\nandrostenedione androgens to estradiol and estrone. Tetranucleotide repeat polymorphism\n(TTTA) n in intron 4 of the  CYP19A1  gene leads to aromatase\nhyperactivity. In general, women with fewer (TTTA) repeats in this gene show lower\nestrogen concentrations which results in susceptibility to unexplained infertility\n( 68 ).\n\nThe purpose of this review was to summarize the factors\nthat have been identified as influencing IVF outcomes.\nWe have reviewed 70 studies that have reported multiple\nfactors involved in IVF treatment. Prior research has focused on a few factors involved in the IVF success rate.\nPredicting the likelihood of pregnancy after IVF can\nhelp stop over-treatment and equilibrate the chances of\nIVF success. In this review, we evaluate 6 predictors, especially genetic factors that can help predict the success\nof IVF. Based on the available literature, we conclude that\nfemale age, BMI, psychological factors, hormonal profiles, sperm characteristics, and genetic factors are predictive factors of IVF success.\nIn this regard, a wide range of factors could be taken\ninto consideration on which a particular emphasis should\nbe placed. As a matter of fact, nutrients are viewed as one\nof the essential factors in IVF success rate. With regard\nto semen quality which is believed to be a vital factor,\nit proves efficient in IVF outcomes. As nutrients play a\nmassive role in the quality of semen, it is of major significance. Therefore, the consumption of nutritional supplements could have innumerable constructive impacts on\nIVF. What is more, Females’ BMI is considered to be an\nintegral element in the serum level of hormones. Consequently, once BMI decreases and takes place in a normal\nrange, the IVF process could have more productivity and\nefficiency in obese women. Due to the fact that sperm\ncharacteristics are regarded as one of the most basic ways\nin order to evaluate the cause of infertility among couples.\nHence, when visiting an infertility center, this factor is of\nmore importance compared to other elements, and it is\nbetter to check sperm-related characteristics first. Moreover, due to unique genetic sequences that vary from person to person, based on their mutations, a unique personal\napproach could be taken into account. This process could\ngive a tremendous boost to the level of IVF success rate.","source_license":"CC0","license_restricted":false}