Enhancing IVF Success in Challenging Infertility Cases: The Role of PRGF, GH, and Endometrial Optimization.

A 35-year-old female with her 40-year-old husband came to the fertility clinic with a history of infertility of 5 years duration. In spite of many attempts at natural conception and three previous cycles of intrauterine insemination (IUI) not a single yielded a positive result. The female underwent hormonal investigations in order to assess her fertility potential. Her AMH level was found to be low, which is a marker of ovarian reserve. Other hormones including luteinizing hormones (LHs) and follicle-stimulating hormone (FSH) were found in a normal range, whereas prolactin levels were found to be slightly elevated as shown in Table 1 but did not indicate hyperprolactinemia. Hormonal profile of female Transvaginal ultrasound (TVUS): A transvaginal ultrasound revealed a thin endometrium (6.5 mm) during the mid-luteal phase. Hysteroscopy: A diagnostic hysteroscopy was performed, which resulted in a slightly irregular endometrial lining with areas of possible scarring, hence suggesting a history of subclinical endometritis. The male partner also underwent a fertility workup which included a semen analysis which was normal. The sperm count, motility, and morphology were all normal, thus showing no abnormality as presented in Table 2 . Also, the hormonal testing including the level of testosterone, FSH, and LH was conducted, and the results demonstrated a normal hormonal profile. Overall, the investigations of the male partner did not reveal any cause of infertility. Semen Parameters of Male An integrated management approach was developed for the patient with a previous history of primary infertility, diminished ovarian reserve, and thin endometrial lining. To increase the likelihood of a successful cycle during IVF, stimulation of the ovaries was begun with gonadotropins and a GnRH antagonist. This protocol was designed to stimulate the growth of follicles for subsequent collection of the eggs. Based on the decreased ovarian reserve, growth hormone (GH) injection was introduced to the stimulation protocol. The GH was given subcutaneously at a dose of 4 IU/day during the whole stimulation cycle to enhance the quality of the oocytes retrieved. GH has been proposed to stimulate ovarian function and benefit embryo quality, which makes it a strategic component. Regarding the patient’s thin endometrial lining, plasma rich in growth factors (PRGF) was applied. PRGF was then prepared from the patient’s blood through centrifugation to obtain a portion containing a high concentration of growth factors as shown in Figure 1 . It was administered intrauterinely during the third week of her menstrual cycle (proliferative phase). The aim was to enhance the endometrial thickness and its receptivity prior to the embryo transfer to provide the best possible setting for implantation in the uterus. Also, endometrial scratching was done in the cycle before IVF treatment. This minor procedure causes controlled damage to the endometrium, which triggers the release of inflammatory cytokines and growth factors that may improve the receptivity of the endometrium. Endometrial scratching was also applied aiming at improving implantation alongside PRGF. PRGF preparation via centrifugation Following ovarian stimulation, six MII oocytes were retrieved and served for intracytoplasmic injection (ICSI), a method intended to improve the rate of fertilization by injecting sperms directly into the cytoplasm of the oocytes. This led to the development of four good-quality blastocysts, from which two were chosen for transfer. Since the patient had previously been diagnosed with a thin endometrial lining, assisted hatching was done on the selected blastocyst. In this process, a small opening is made on the outer layer (zona pellucida) of the embryo to assist hatching so that it would have better chances of implanting on the uterus wall. The patient was advised to rest for a few hours in the clinic after the embryo transfer in order to minimize discomfort after ET. The doctor prescribed her to refrain from participating in any heavy undertaking, vigorous exercise, lifting heavy objects, and any strenuous activities for the next few days. However, moderate physical activity that included walking and regular domestic activities was allowed. The patient was counseled to come for a follow-up blood test after 2 weeks following the embryo transfer in order to check on pregnancy. The test result indicated a positive sign for pregnancy with the β-hCG level of 256 ng/ml; then the female was advised to follow a healthy lifestyle and continue taking prenatal vitamins. Also, she was instructed to get enough sleep, engage in light exercise like walking, and avoid heavy lifting and strenuous work. She was also advised to report any signs of complications like bleeding and continued and severe spasms and not to take alcohol, practice smoking, and excessively caffeinated products.

Infertility is a condition affecting millions of couples worldwide and defined as failure to achieve pregnancy after 1 year or more of nonprotected sexual intercourse. Around 15% of infertile couples have unexplained or unidentified causes, while in 85% of couples, the cause of infertility is identified. Lifestyle and environmental factors, such as obesity and smoking, can adversely affect infertility. Tubal disease, ovulatory dysfunction, and male factor infertility are the most common causes of infertility. Around 70% of women with anovulation have polycystic ovary syndrome: Ovulatory disorders contribute to around 25% of infertility diagnoses.[ 1 ] Endometritis, pelvic inflammatory disease (PID), and bacterial vaginosis are genital tract infections that may cause infertility. Both PID and endometritis are caused by the migration of pathogenic bacteria into the uterus; the processes by which the bacteria move and cause infection are not fully understood.[ 2 ] Endometritis is characterized by infection or inflammation of the endometrium and can be classified into two types: acute and chronic. Acute endometritis is characterized by obvious signs of inflammation, and the histology shows microabscesses and neutrophil infiltration of the superficial endometrium. On the other hand, chronic endometritis (CE) may not cause any symptoms and is usually detected during the assessment of secondary amenorrhea or infertility. The acute and chronic forms of endometritis have been associated with adverse reproductive consequences.[ 3 ] Recent research findings contradict previous perceptions of CE as a mild or insignificant disease, revealing its significant impact on reproductive capacity. CE negatively affects endometrial receptivity, which results in increased infertility, implantation failure, and recurrent pregnancy loss (RPL). The live birth rate is significantly low in women with untreated CE and RPL history; the percentage is about 7%. Nevertheless, evidence suggests that antibiotic administration and elimination of inflammation can greatly improve pregnancy outcomes.[ 4 ] A receptive endometrial lining is required for the successful implantation of embryos, but it is usually impaired in patients with thin endometrial lining or conditions such as endometritis.[ 3 ] Plasma-rich growth factors (PRGF) therapy stimulates endometrial growth with a biochemical pregnancy rate of 59% and an ongoing pregnancy rate of 48%. The PRGF success rate is significantly higher when it is infused after 6.5 and 9.5 days of the menstrual cycle. PRGF is a safe and cost-effective treatment that helps to optimize the endometrium as well as embryo–maternal communication.[ 5 ] Endometrial scratching on the other hand is a relatively simple process that involves creating small scratches on the surface of the endometrium. Some studies support the fact that this treatment can increase the live birth rate if performed before the first cycle of in vitro fertilization (IVF).[ 6 ] The concept of performing endometrial scratching prior to embryo transfer has been proposed as a measure that may increase implantation rates. The procedure seems to be most helpful in cases of women who have previous records of implantation failure and seems to improve the chances of a successful pregnancy.[ 7 ]

This case study demonstrates the effectiveness of a personalized and multifaceted approach to IVF in addressing complex infertility issues. Incorporating PRGF and GH supplementation along with endometrial scratching and assisted hatching into the treatment plan improved the odds of implantation and thus pregnancy in the course of treatment. The successful IVF results underscore the importance of customized infertility treatment according to the patient’s need, showing how tailored methods can improve IVF outcomes in even difficult cases. In general, this case is beneficial for identifying new distinct approaches to treat infertility and should inspire researchers to further study similar concepts. There are no conflicts of interest.

In this case, personalized IVF treatment plans with PRGF, GH, and other supportive treatments have been shown to be very useful, indeed, because the patient has a history of primary infertility, low reserve, and thin endometrial lining pose serious challenges in conceiving. However, the customized action plan contributed to the positive result. PRGF played a key role in enhancing endometrial receptivity. Given before the embryo transfer, PRGF probably enhanced the receptivity of the uterus, thereby enhancing implantation. Emerging research supports PRGF’s ability to improve implantation rates in patients with thin endometria, a critical factor in this case. GH was administered during ovarian stimulation to enhance follicular development and oocyte quality because of the patient’s low ovarian reserve as well as to enhance fertilization chances and embryo growth. Endometrial scratching carried out in the cycle before IVF brought extra benefits to endometrial receptivity. This procedure created a mild controlled injury on the uterine lining that stimulated the favorable inflammatory response as well as the release of growth factors to increase chances of the implantation. In order to increase the chances of successful implantation, assisted hatching was done. This was especially useful in cases where the endometrial layer is thin, thereby improving the interaction between the embryo and the endometrial lining. Despite the patient’s reproductive challenges, the combination of these targeted interventions resulted in a positive pregnancy outcome. This case illustrates how PRGF, GH, and other adjunctive therapies can be utilized in solving difficult infertility problems and enhancing the chances of IVF success through patient-tailored methods. According to a study done by Yidi Wang et al. ,[ 8 ] thin endometrium is associated with impaired assisted-reproductive treatment outcomes. Also, thin endometrium affects endometrial tolerance, leading to lower embryo implantation rates and clinical pregnancy rates. However, Yuye Li et al .[ 9 ] in their recent study evaluated the relationship between pregnancy outcome and chronic endometriosis and found that the patients with RIF and chronic endometriosis have noticeably lower pregnancy rates. In the study conducted by D Bodri et al. ,[ 10 ] PRGF showed a significant improvement in the pregnancy rate, especially in patients with thin endometrium and RIF. According to them, PRGF also reduced the chances of recurrent miscarriages and led to positive pregnancy. Similarly, Jon Ander Agirregoikoa et al .[ 5 ] stated that PRGF enhances the endometrium and improves the pregnancy outcome. This therapy enables successful implantation of the embryo in the uterus and is comparatively safe, easily accessible, and inexpensive.