Dose Of Human Menopausal Gonadotrophin Research Articles

Progestin-primed ovarian stimulation protocol with or without clomiphene citrate for poor ovarian responders: a retrospective cohort study

ObjectiveTo explore the efficacy of progestin-primed ovarian stimulation (PPOS) combined with clomiphene citrate (CC) versus PPOS protocol used alone on cycle characteristics and pregnancy outcomes for women with the poor ovarian response (POR).MethodsWe performed a retrospective cohort study and a total of 578 POR patients who underwent IVF/ICSI cycles were collected and divided into Group A (HMG 300 IU/d + MPA 10 mg/d) and Group B (HMG 300 IU/d + MPA 10 mg/d + CC 50 mg/d). The primary outcome measure was the number of oocytes retrieved, other outcome measures were cycle characteristics and clinical pregnancy rate.ResultsThe baseline information between the two groups were not statistically significant (P > 0.05). Compared with Group A, Group B had a lower total dose of human menopausal gonadotrophin (HMG) (2998.63 ± 1051.09 vs. 3399.18 ± 820.75, P < 0.001) and the duration of stimulation (10.21 ± 3.56 vs. 11.27 ± 2.56, P < 0.001). Serum luteinizing hormone level was higher in Group B on human chorionic gonadotrophin injection day (P < 0.001). The number of oocyte for retrieval, maturation, and fertilization were significantly lower in Group B than that in Group A (P < 0.001). However, the oocyte retrieval rate, maturation rate, fertilization rate, and viable embryo rate showed no statistical difference in the two groups (P > 0.05). After adjusting for confounders, the clinical pregnancy rate (OR 1.286; 95% CI 0.671–2.470) and live birth rate (OR 1.390; 95% CI 0.478–3.990) were comparable between the two groups.ConclusionsPPOS protocol combined with CC reduces the total dose of HMG and the duration of stimulation, and can also achieve similar oocyte yields and clinical pregnancy rate compared with the PPOS protocol used alone in poor ovarian responders.

Mild Ovarian Stimulation for Infertility in Women with Polycystic Ovary Syndrome

Objective: The aim of this study was to explore the effect of clomiphene citrate (CC) on the cycle characteristics and outcomes of women with polycystic ovarian syndrome (PCOS) undergoing ovarian stimulation. Methods: This is a cross sectional study, and it was conducted at the tertiary-care medical center. This study included 55 PCOS patients and 54 patients without PCOS undergoing ovarian mild stimulation. In the study group (n = 55), CC and human menopausal gonadotropin (HMG) were administered simultaneously beginning on cycle day 3, while in the control group without PCOS (n = 54) a differing protocol treatment was used. The primary outcome measure was the stimulation day, HMG dose, number of dominant follicles, serum E2, LH, P4 in trigger day and number of oocytes. Secondary outcomes included the number of top-quality embryos, maturation rate, fertilization rate, cleavage rate, incidence of premature LH surge, and OHSS, biochemical and clinical pregnancy rate. Results: The study group received obviously a lower total HMG dose [470.54 ± 304.5 (375–975) vs. 500.00 ± 287.59 IU, but similar HMG duration. While the antral follicle count (AFC) was higher in the study group, the number of oocytes retrieved and top-quality embryos was remarkably less [5 (0 – 30) vs. 13 (0 – 42), 2 (0 –14) vs. 3.5 (0 – 15), p = 0.003, respectively]. The mature oocyte rate was higher in the study group (p = 0.036). No significant differences were detected in fertilization rate and cleavage rate between the 2 groups. CC had a positive influence (higher oocytes retrieved and top-quality embryos) on cycle characteristics, but might be correlated with the impaired IVF outcomes (lower E2, lower implantation rate) in PCOS patients undergoing IVF, when CC + HMG was used simultaneously. Conclusion: In women with PCOS, mild CC stimulation resulted in increased oocytes and viable embryos compared with the control group. The study regimens had a low incidence of OHSS. The results of the CC combined regimen provide new insights into the development of a more patient-friendly protocol for women with PCOS. However, this study needs to be continued on more samples in the future.

What are the factors affecting IVF success in women with hypogonadotropic hypogonadism?

This study aimed to investigate in vitro fertilization (IVF) outcomes in women with hypogonadotropic hypogonadism (HH) and unexplained infertility and investigate factors affecting the pregnancy rate among HH patients. This retrospective cohort study was conducted at Zeynep Kamil Maternity and Children's Diseases Training and Research Hospital, Turkey, a tertiary care referral center. The medical records of 143 women who underwent IVF treatment at this hospital between 2015 and 2020 were reviewed. Sixty-three had hypogonadotropic hypogonadism (HH) and 74 had unexplained infertility. Demographics, hormonal profile, IVF cycle characteristics, and pregnancy rates were recorded. The factors affecting the ongoing pregnancy rates were evaluated among HH patients. Anti-Mullerian hormone (AMH) levels were lower among women with HH compared to those with unexplained infertility (1.64±1.2 vs. 3.0±2.13). IVF cycle characteristics and ongoing pregnancy outcome (20.28% vs. 22.97%) were similar between the groups; however, the total dose of human menopausal gonadotrophin (HMG) used (5127.74±1845.8 vs. 2035.71±1387.45) was higher in the HH group. Increased estradiol level (2596.35±1085 vs. 1869.9±1203.4), endometrial thickness (10.82±1.74 vs. 8.43±2.33), higher number of total oocytes retrieved (12.14±4.34 vs. 8.43±5.44) were correlated with higher ongoing pregnancy rates among the HH group. IVF success rates were similar between the HH and unexplained infertility groups. Although AMH level was not a prognostic factor for IVF success, higher doses of HMG were needed to achieve pregnancy in the HH group. The factors affecting the ongoing pregnancy rates in the HH group were higher estradiol level, increased endometrial thickness, and a higher number of oocytes retrieved.

BODY MASS INDEX IN PATIENTS WITH POLYCYSTIC OVARIAN SYNDROME AND ITS RELATION TO DOSE AND DURATION OF HMG, OVULATION RATE AND PREGNANCY RATE

Background: Polycystic ovary syndrome (PCOS) is one of the most common causes of endocrinological disorders affecting 5-10% of women in reproductive age. It is the most important cause of anovulation and infertility. Objective: To examine the relation of body mass index in PCOS patients with dose and duration of Human Menopausal Gonadotropin (HMG), ovulation rate and pregnancy rate. Patients and Methods: The study was retrospectively conducted on 150 women selected from patients attending the infertility clinic of Al-Azhar hospitals, Faculty of Medicine, Al-Azhar University during the period from August 2018 till July 2020, and we revised and collected that data from the records. All cases were selected after fulfilling inclusion and exclusion criteria. The patients were divided into three equal groups according to their body mass index, Group A: patients with normal body mass index (BMI 19-24.9), Group B: patients with overweight (BMI 25-29.9) and group C: patients with obesity (BMI equals or more than 30). Results: There was a statistical significance as regards pregnancy rates between studied groups. In the current study there was a statistical significant difference between three groups as regards the mean age. There was no statistical significant difference between three groups as regards the mean Follicular Stimulating Hormone (FSH), Luteinizing Hormone (LH), Estradiol (E2), Prolactin (PRL) and Thyroid stimulating Hormone (TSH). According to the days of stimulation, group C showed a significant increase than group A and B. The dose of HMG used in the three studied groups, showed a significantly higher dose used in group C than group A and B. The ovulation rate was 68% in group A, 56% in group B and 28% in group C. The results were compared with other studies of similar scope and most of them were recent ones. In our study, obesity had negative impact on ovulatory functions. It seemed that obesity was a negative prognostic factor for women referred to vitro fertilization (IVF) treatment. They should be encouraged to change lifestyle habits in order to lose weight before starting fertility treatment. Although our findings did not support a policy of excluding obese and overweight women from IVF treatment on the grounds of likely failure of ovulation induction or IVF, Beyond the IVF results, obesity increased morbidity for both mother and fetus. There was an increased risk in pregnancy hypertension, toxemia, gestational diabetes, Cesarean section, increased hospitalization, and the risk to their offspring of their abnormality in BMI. Conclusion: Programs of weight loss are recommended for obese women undergoing in vitro fertilization, and the institution of a process of weight loss where appropriate, HMG can be given to patients with PCO adjusting dose according to their BMI and response with expecting satisfactory ovulation, and pregnancy rate.

Progesterone affects clinic oocyte yields by coordinating with follicle stimulating hormone via PI3K/AKT and MAPK pathways

IntroductionAs an effective inhibitor of premature ovulation, progestin was introduced to a novel ovarian stimulation regimen for infertility treatment. However, the local action of progestin on the ovary and its effect on clinical outcomes have not been described. ObjectivesThe influence of progesterone administration on clinical oocyte outcomes and the mechanisms involved in the coordination of progesterone and follicle stimulating hormone (FSH) on follicle growth and oocyte yields were investigated. MethodsClinical outcomes of patients undergoing ovarian stimulation for in vitro fertilization were analyzed. The murine ovarian stimulation model and follicle culture system were used to evaluate the effects of progesterone on oocyte yield, follicle development, granular cell proliferation, and hormone secretion. Phospho-specific protein microarrays were used to explore involved signaling pathways. ResultsProgesterone decreased clinical oocyte yields, and yields were rescued with an increased dose of human menopausal gonadotropin. Administration of progesterone inhibited murine granular cell proliferation and reduced the growth rate of follicles; both of which were rescued by FSH. The phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) were identified as pivotal signaling pathways to integrate progesterone into the FSH signaling network in granular cells. ConclusionProgesterone inhibited granular cell proliferation and antral follicle growth during ovarian stimulation, and subsequently influenced oocyte outcomes in the clinical setting. Progesterone coordinated with FSH to regulate follicle growth through PI3K/AKT and MAPK signaling pathways. These findings advance our knowledge regarding the ovarian response to gonadotropins during progestin-primed ovarian stimulation and create an opportunity to manipulate individual oocyte yields.

The effect of different endometrial preparations on women with polycystic ovary syndrome undergoing initial frozen embryo transfer: A historical cohort analysis.

Frozen embryo transfer is associated with a higher rate of live birth and a lower risk for ovarian hyperstimulation syndrome in women with polycystic ovary syndrome (PCOS) compared with fresh embryo transfer. The aim of this study is to assess the optimal endometrial preparation protocol for women with PCOS undergoing frozen embryo transfer. We conducted a historical cohort analysis of 1720 women with PCOS who underwent the "freeze-all" strategy between August 2014 and August 2017 because of their high risk for ovarian hyperstimulation syndrome. Three endometrial preparation protocols were used: natural cycle (NC; n=191), which relies on the dominant follicle to secrete estrogen that then promotes endometrial growth; ovarian stimulation (OS; n=96), which induces follicle growth using low doses of human menopausal gonadotropin; and hormone replacement (HRT; n=1433), which uses exogenous estradiol to promote endometrial growth. The primary outcome was live birth. For women who received a single embryo transfer, the live birth rates for the NC, OS, and HRT groups were 62.4%, 65.0%, and 52.2%, respectively. The live birth rate in the HRT group was significantly lower than that seen in the OS and NC groups (P=.009). The clinical pregnancy rates of the three groups were 72.3%, 73.8%, and 64.9%, respectively; this difference did not reach statistical significance (P=.071). The rate of live birth with the NC and OS regimens was higher than with the HRT protocol in women with PCOS who undergo single-blastocyst frozen embryo transfer.

Effect of Progestin-Primed Ovarian Stimulation Protocol in Infertile Women with Basal Follicle-Stimulating Hormone Levels ≥15 IU/L: A Retrospective Analysis

Objective: To evaluate the efficacy of progestin-primed ovarian stimulation (PPOS) protocol in infertile women with high basal follicle-stimulating hormone (FSH) levels ≥15 IU/L. Methods: Patients with high basal FSH levels ≥15 IU/L with autologous oocytes from September 2016 to March 2019 were reviewed. Either medroxyprogesterone acetate 4 mg/d or clomiphene citrate (CC) 50 mg/d was administered daily from day 3 to the trigger day. When serum FSH levels decreased to ≤15.0 IU/L, a low dose of human menopausal gonadotropin (hMG) 75/150 IU/d was administered to promote late follicular development. Results: Two hundred and twenty women were retrospectively analyzed in this study. Among them, 139 patients were administered with PPOS protocol as the study group, and 81 patients were administered with CC protocol as the control group. The numbers of received oocytes and viable embryos were higher in the study group than those in the control group (1.5 ± 1.2 vs. 1.2 ± 0.8 and 0.8 ± 0.8 vs. 0.5 ± 0.6, respectively, P < 0.05). However, hMG duration and dosage were significantly higher in the study group than those in the control group (4.2 ± 2.7 d vs. 1.1 ± 2.3 d and 609.1 ± 424.5 IU vs. 140.7 ± 231.3 IU, respectively, P < 0.01). Incidence of luteinizing hormone surge and cycle cancellation rate were lower in the study group than those in the control group with statistical difference (2.88% vs. 16.05% and 36.50% vs. 50.63%, respectively, P < 0.05). Conclusions: PPOS protocol can effectively downregulate the endogenous FSH levels. Compared with CC protocol, treatment with PPOS protocol in patients with high basal FSH levels ≥15 IU/L could receive more oocytes and more viable embryos.

Progesterone Affects Clinic Oocyte Yields by Coordinating with FSH &lt;i&gt;via&lt;/i&gt; the PI3K/AKT and MAPK Pathways

Background : Over recent years, progestin has been incorporated into the novel ovary stimulation regimens as an alternative for GnRH analogs to prevent premature luteinizing hormone surge, and has become widely used in treatment for infertility. However, the influence of progesterone administration in terms of clinical outcomes and the mechanisms involved remains poorly understood. Methods: The clinic outcomes from patients undergoing ovary stimulation for in vitro fertilization were analyzed. The mouse ovary stimulation model and follicle culture system were used to evaluate the effect of progesterone on oocyte yield, follicle development, granulosa cell proliferation, hormone secretion. Phospho-Specific Protein Microarray, western blot and RT-PCR were employed to explored the signal mechanism. Findings: We present the evidence from patients suggesting that progesterone decreased the oocyte yields, that was rescued by the higher dose of human menopausal gonadotropin. Using both in vivo and in vitro mouse models, we demonstrated that the administration of progesterone inhibited the proliferation of granulosa cells and therefore reduced the growth rate of follicles. The action of progesterone was mediated by progesterone receptor membrane component-1 and rescued by FSH. Using a phosphorylation array, we identified the PI3K/AKT and MAPK are pivotal pathways that integrated the action of progesterone into the FSH signaling network via the downregulation of cyclin D2 and c-fos in granulosa cells. Interpretation: Our findings highlight the mechanism by which progesterone coordinates with FSH to regulate follicle growth and subsequently influence oocyte outcomes in clinic. These findings advance our understanding of the alterations of ovary response to gonadotrophins during progestin primed ovarian stimulation and gives rise to the opportunity for manipulating individual oocyte yields by signaling regulation. Funding Statement: This study was financially supported by the Natural Science Foundation of Shanghai (Grant number 19ZR1429300, awarded to HL), research grants from the National Natural Science Foundation of China (Grant number 81871163, awarded to QL; Grant number 81771533, awarded to YK; Grant number 81671520, awarded to QC), and the National Key Project (Grant number 2018YFC1003000). Declaration of Interests: The authors have declared that no conflict of interest exists. Ethics Approval Statement: Approval for human retrospective analysis was obtained from the institutional Ethics Committee of Shanghai Ninth People’s Hospital affiliated to Shanghai JiaoTong University’s School of Medicine. Animal studies were approved by the institutional Ethics Committees of Care and Use of Experimental Animals of Shanghai Jiaotong University.

The effects of low-dose human chorionic gonadotropin combined with human menopausal gonadotropin protocol on women with hypogonadotropic hypogonadism undergoing ovarian stimulation for in vitro fertilization.

To investigate the effects of low-dose human chorionic gonadotropin (hCG) combined with human menopausal gonadotropin (HMG) protocol on cycle characteristics and outcomes of infertile women with hypogonadotropic hypogonadism (HH) undergoing ovarian stimulation for in vitro fertilization (IVF). A retrospective cohort study. Tertiary-care academic medical centre. Forty-six infertile patients with HH and seventy-one infertile patients with tubal factor (TF) infertility undergoing IVF. In the study group, all 46 HH patients were given low-dose hCG (50-300IU/d) in combination with HMG daily from cycle day 3. Meanwhile, a control group consisting of 71 patients with tubal factor infertility was set up, where the infertile women were given triptorelin 3.75mg on cycle day 3 for desensitization and started stimulation with HMG only 5weeks later. Transvaginal ultrasound and serum sex steroids were used for monitoring the development of follicles. Ovulation was triggered by hCG 5000IU when dominant follicles matured. Viable embryos were transferred on the third day after ovum pickup or cryopreserved for later transfer. The primary outcome measure was the clinical pregnancy rate. Secondary outcomes included hCG day P4, ratio of E2/follicle count, number of oocytes retrieved, number of viable embryos, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate. With lower basal FSH, LH and E2, HH patients showed longer HMG stimulation duration (13 (10-22) d vs 12 (8-18) d, P<.001) and higher HMG dose (2960±560 IU vs 2663±538 IU, P=.005). Whilst the antral follicle count (AFC), number of follicles with diameters greater than 10mm on trigger day and oocytes retrieved were less in the HH group, the number of follicles with diameters greater than 14mm and viable embryos were comparable. The ratio of E2/follicle count (>10mm) and E2/follicle count (>14mm) were distinctively higher in the HH group (1056±281 vs 830±245, P<.001; 1545±570 vs 1312±594pmol/L, P=.037; respectively). The clinical pregnancy rate, implantation rate, ongoing pregnancy rate and cumulative pregnancy rate per woman were comparable between the two groups. Comparison among the subgroups with different hCG dosage showed that HMG duration shortened with the increase of daily hCG dose (14.84±2.88 vs 13.96±2.63 vs 12.96±1.30days, P=.037). No significant differences were detected in outcomes between fresh embryo transfer (ET) group and frozen-thawed embryo transfer (FET) group. Low-dose hCG combined with HMG is a feasible protocol for HH women undergoing ovarian stimulation in IVF, providing favourable cycle characteristics and pregnancy rates. Low-dose hCG reduces HMG duration, whilst the hCG dose and embryo quality are not positively correlated. The outcomes of FET are comparable to ET, which provides a greater chance of success from IVF in the low responders with HH.

The role of gene polymorphisms and AMH level in prediction of poor ovarian response in Egyptian women undergoing IVF procedure.

The aim of this study is to assess the role of AMH in prediction of poor ovarian response as well as the relation between ESR 2 (+1730G>A) (rs4986938) and FSHR p.Thr307Ala (c.919A>G, rs6165) SNPs and the poor ovarian response in Egyptian women undergoing IVF procedure. Discovering the genetic variants associated with ovarian response is an important step towards individualized pharmacogenetic protocols of ovarian stimulation. We performed a prospective study on 216 young women with unexplained infertility. Ovarian stimulation was performed according to the GnRH antagonist protocol with a fixed daily morning dose of human menopausal gonadotrophin (HMG). The estrogen receptor (ESR2) (+1730G>A) (rs4986938) and FSH receptor p.Thr307Ala (c.919A>G, rs6165) single nucleotide polymorphisms (SNPs) were detected by real-time polymerase chain reaction. Serum FSH, Estradiol (E2) and anti-Müllerian hormone (AMH) levels were measured by enzyme-linked immunosorbent assay (ELISA). This study revealed that the low AMH level was highly significantly related to the poor ovarian response (p<0.001). Furthermore, the frequency of the ESR2 (AA) genotype and the FSHR (Ala307Ala) genotypes were highly significantly associated with the poor ovarian response (p<0.001). The AMH level in combination with the ESR2 and the FSHR gene polymorphisms predict the poor ovarian response to COH in Egyptian women. ClinicalTrials.gov Identifier: NCT02640976.

Ovarian sensitivity index is a new cost-effective parameter for ovarian responsiveness in an IVF/ICSI cycle

Objective The aim of this study was to validate the use of the ovarian sensitivity index (OSI) in predicting ovarian response and thus calculating the optimal human menopausal gonadotropin dose to reach a desirable ovarian response in invitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Study design This study was an observational one. Setting The study was conducted in University Hospital IVF Center. Patients A total of 731 patients undergoing IVF/ICSI treatment cycle were included in the study. Results The OSI correlated with ovarian reserve parameters, positively with antral follicle count and anti-Müllerian hormone, and inversely with follicle stimulating hormone, age, and BMI (P<0.001 for all except BMI, for which P=0.018). Moreover, the OSI showed a significant inverse correlation with ovarian response parameters: the total dose of gonadotropin administered, average daily dose of gonadotropin, and duration of stimulation (P<0.001). Conclusion The OSI is a reliable parameter for ovarian responsiveness and can be used to calculate the optimal human menopausal gonadotropin dose to reach a desirable ovarian response in ICSI cycles.

Series of 18 Cases of Clomiphene Resistant Anovulatory Women with Polycystic Ovary Syndrome and Altered Response to FSH Stimulation

The outcome of ovulation induction in anovulatory polycystic ovarian syndrome (PCOS) may depend, in part, on the pharmacologic compounds used, but also on individual patient characteristics, such as age, body mass index (BMI), hyper- androgenism, luteinizing hormone (LH), hyper-secretion, anti mullerian hormone (AMH) levels and possibly antral follicle count (AFC) with ovarian volume of these women. There exists a subset of clomiphene citrate (CC) resistant PCOS women who require stimulation of ovulation with high doses of human menopausal gonadotropin (hMG), after not having responded to chronic low dose step up regimes of recombinant follicle stimulating hormone (r-FSH).

Clinical outcomes of three- or five-day treatment with clomiphene citrate combined with gonadotropins and a timed intercourse cycle in polycystic ovary syndrome patients.

ObjectiveThis study aimed to investigate the effect of a new clomiphene citrate (CC) regimen on preventing thin endometrial lining in polycystic ovary syndrome (PCOS) patients receiving CC plus gonadotropin treatment with a timed intercourse cycle.MethodsA total of 114 women with PCOS were included in this trial. Patients were divided into two groups and treated in accordance with the controlled ovarian stimulation (COS) protocol. In group A, 104 COS cycles in 67 patients were included, and in each cycle 150 mg CC was given for three days, starting from day 3. In group B, 69 COS cycles in 47 patients were included, in which 100 mg CC was given for five days, starting from day 3. The thickness of the endometrium was measured on the day of human chorionic gonadotropin (hCG) injection. Timed intercourse was recommended at 24 and 48 hours after the hCG injection.ResultsAdditional doses of human menopausal gonadotropin and the number of days of hCG administration were not significantly different between the two groups. Endometrial thickness on the day of hCG administration was significantly larger in group A than group B (9.4±2.1 mm vs. 8.5±1.7 mm, p=0.004). The pregnancy rate was significantly higher in group A than in group B (38.4% vs. 21.7%, p=0.030).ConclusionThree-day CC treatment resulted in a significantly higher pregnancy rate than the standard five-day CC treatment in a timed intercourse cycle in PCOS patients. Facilitating adequate endometrial growth via the early discontinuation of CC might be a crucial factor in achieving a higher pregnancy rate.

Comparison of IVF/ICSI outcome in patients with polycystic ovarian syndrome or tubal factor infertility

One of the recognized treatment options for patients with polycystic ovarian syndrome (PCOS) is in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Fears are however sometimes raised concerning the likely outcome of treatment in such patients compared with their counterparts with tubal factor infertility. To compare the IVF/ICSI performance in women with PCOS and those with tubal factor infertility. A retrospective analysis. Case notes of 30 patients, 35 years and below, with PCOS and who underwent 33 IVF/ICSI cycles and those of 42 age-controlled patients with tubal factor infertility and who had 43 cycles between December 2004 and April 2008 were retrieved. Data including duration of down-regulation, dose of human Menopausal Gonadotropin (hMG), number of cancelled treatments, endometrial thickness, number of oocytes retrieved and fertilization rate, in addition to the number of embryos transferred with resultant pregnancy outcome were compared between the two groups. The main outcome measures were response to gonadotropin stimulation, fertilization rate and clinical pregnancy rate. There was no significant difference between the PCOS group and the tubal factor infertility group in the hMG dose (2.7 vs. 3.4 vials, respectively), endometrial thickness (10.5 vs. 10.1 mm, respectively) and embryos transferred (3.1 vs. 2.9, respectively). The fertilization rate was significantly higher in the tubal factor infertility group, which was 81.48% as against 63.24% for the PCOS group ( P < 0.0001). While more cases of ovarian hyperstimulation syndrome (OHSS) occurred in the PCOS group ( P = 0.049), overall clinical pregnancy rate per embryo transfer was similar (45.45% vs. 42.85%; P = 1), with similar miscarriage rates. IVF/ICSI performance in patients with PCOS is probably similar to their counterparts with tubal factor infertility with, however, a reduced fertilization rate and higher incidence of OHSS.

Affordable ART: a different perspective

Although ≈ 10% of the population is affected by infertility, the treatment option of in-vitro fertilisation (IVF) remains unaffordable for the majority of infertile couples. We have initiated a lowcost programme incorporating an uncommonly used, but recognized, ovarian stimulation protocol, together with certain costlimiting initiatives in an established assisted reproductive technology (ART) set up. The medical records of women who underwent the lowcost programme were analysed. Clomiphene citrate 50 mg daily was administered from Day 2 of the cycle and continued till the day of hCG trigger, thus preventing the LH surge. Intermittent doses of human menopausal gonadotrophin 150 IU were administered on alternate days from the 5th day onwards. Oocyte retrieval was carried out once at least two follicles of >18 mm were identified. The cycle was monitored by ultrasound only, with embryo transfer being carried out on Day 3. Clinical outcomes were recorded together with an estimation of the direct costs per cycle. Direct cost calculations did not include professional charges or facility costs. Of 143 women evaluated, 104 women underwent embryo transfer. The live birth rate and clinical pregnancy rate per embryo transfer were 19 and 22%. The live birth rate per initiated cycle was 14% (20/143). The multiple pregnancy rate was 26% with no case of ovarian hyperstimulation syndrome being recorded. The average direct cost per cycle was US$ 675 for IVF and US$ 725 for an ICSI treatment cycle. Using this protocol, together with several costcutting measures, we achieved an acceptable live birth rate per transfer of 19% at a reasonable cost. This approach could be used by established ART centres to provide treatment to couples who cannot afford conventional ART.

Implantation Techniques

ABSTRACT Decades of research and improving technology have taken in vitro fertilization techniques to a highly sophisticated level. Attention in the later twentieth century was increasingly paid to the endocrine stimulation of follicle growth and oocyte maturation. Hormonal stimulation became more complex. Methods for ovarian hyperstimulation became complex. GnRH agonists and antagonists came into play to provide a better control over FSH and LH concentrations during follicular and luteal phases of stimulated cycles including the correction of premature LH surges. A lot of stress is being paid nowadays on natural remedies to replace the high tech treatment modalities and so also evolved the so called natural cycle in vitro fertilization, the drug free or minimal drug fertility treatment. There are opinions worldwide of experts that the methods that are currently being used for ovulation and to stimulate growth of the follicle in infertile women are too expensive in addition to being extreme measures. Not only are they costly but the effect on the human body has given rise for the need for a more nature-friendly method. Alternative approaches are therefore being sought including minimal stimulation IVF, natural cycle IVF and maturing human oocytes in vitro to prepare them for fertilization in vitro. Each of these approaches avoids the use of large doses of human menopausal gonadotrophin (HMG) that have become essential for routine IVF. This article reviews the available literature on these methods and also their fallacies, if any.

Recombinant human follicle-stimulating hormone produces more oocytes with a lower total dose per cycle in assisted reproductive technologies compared with highly purified human menopausal gonadotrophin: a meta-analysis

BackgroundHuman menopausal gonadotrophins and recombinant human follicle stimulating hormone are the two main gonadotrophin products utilized for controlled ovarian stimulation in assisted reproductive technologies. In this meta-analysis, the number of oocytes was designated as the most relevant endpoint directly resulting from ovarian stimulation, and therefore where the drug effect may be estimated with the best sensitivity.MethodsAll published randomized controlled trials on ovarian stimulation comparing the two gonadotrophin products were evaluated. Internal validity was determined using Chalmers' validated scale. If trials did not meet the established quality criteria, a sensitivity analysis assessed the stability of the results. The comparison of continuous variables was conducted following the weighted mean difference and the standardized mean difference (Cohen's effect size) with the random model. Given the known relationship of baseline conditions on treatment endpoints, results were adjusted for age, body mass index and type of infertility.ResultsSixteen studies involving 4040 patients were included. Treatment with human menopausal gonadotrophins resulted in fewer oocytes (-1.54; 95% CI: -2.53 to -0.56; P < 0.0001) compared to recombinant human follicle-stimulating hormone. When adjusting for baseline conditions, the mean difference estimate was -2.10 (95% CI: -2.83 to -1.36; P < 0.001). A higher total dose of human menopausal gonadotrophin was necessary (mean difference, 235.46 IU [95% CI: 16.62 to 454.30; P = 0.03]; standardized mean difference, 0.33 [95% CI: 0.08 to 0.58; P = 0.01]). The pregnancy absolute risk difference (RD [hMG-r-hFSH]) for fresh transfers was 3% (P = 0.051), and the relative risk 1.10 (P = 0.06). When adjusted for baseline conditions, the relative risk was 1.04 (P = 0.49) and absolute difference was 0.01 (P = 0.34), respectively.ConclusionsBecause baseline conditions are predictive of outcome, meta-analytic results are more sensitive when these variables are considered. Using an endpoint closely associated with the stimulation period, sufficient sensitivity is achieved to compare gonadotrophin treatments. As the largest meta-analysis published to date on this subject, treatment with human menopausal gonadotrophins is characterized by fewer oocytes and a higher total dose. When considering only fresh transfers, pregnancy rates were similar.

Outcomes after early or midfollicular phase LH supplementation in previous inadequate responders

Second cycle outcomes of 75 patients who had previous inadequate ovarian response with recombinant FSH (rFSH)-only ovarian stimulation during gonadotrophin-releasing hormone analogue (GnRHa) down-regulated cycles were evaluated retrospectively. In these second cycles, both rFSH and human menopausal gonadotrophin (HMG) in GnRHa long down-regulation were given to all patients, HMG initiated either on day 1 (group A, n=37) or day 5-6 of the ovarian stimulation (group B, n=38). Total HMG dose was higher (1198+/-514 IU versus 726+/-469 IU; P<0.001), cumulative rFSH consumption was lower (1823+/-804 IU versus 2863+/-1393 IU; P=0.001) and duration of stimulation was shorter (8.94+/-1.15 days versus 10.37+/-1.80 days; P<0.001) in group A than in group B. No significant differences were found regarding fertilization, implantation or pregnancy rates and embryo quality between the groups. Further analysis by supplementary HMG dose (75 IU versus 150 IU) revealed that total gonadotrophin and HMG consumption was lower in 75 IU-supplemented subgroups. Notably, pregnancy rate was higher in patients where 75 IU HMG was supplemented on day 5-6 of ovarian stimulation, which deserves further evaluation.

Flexible, Multi-dose GnRH Antagonist versus Long GnRH Agonist Protocol in Poor Responders: A Randomized Controlled Trial

Background: To compare a flexible, multi-dose GnRH antagonist protocol with a long GnRH agonist protocol in poor responders. Materials and Methods: A randomized clinical trial of 70 poor responder patients (35 patients in GnRH antagonist protocol and 35 patients in long GnRH agonist protocol) was performed at Royan Institute, Tehran, Iran. Both groups were given a fixed dose of human menopausal gonadotropin (HMG) for stimulation and oral contraceptive pre-treatment. Data analyzed by student's group t-test or Chi square test. Results: Stimulation duration, total gonadotrophins consumption, mean numbers of oocytes retrieved, formed embryos, cycle cancellation rate, and clinical pregnancy rate were similar between both groups. Although the miscarriage rate was higher in the agonist protocol group, the rate of miscarriage was not statistically significant between both groups. Conclusion: A flexible, multi-dose GnRH antagonist protocol appears as effective as the long GnRH agonist protocol in poor responders. More (larger) randomized controlled trials for better statistical analysis are recommended.

A novel mutation in exon8 of the follicle-stimulating hormone receptor in a woman with primary amenorrhea

The FSH receptor (FSHR) gene mutation are rare, but recently have been detected in several cases with primary amenorrhea. We report a 25-year-old female who had primary amenorrhea, moderately developed secondary sex characteristics and normal sized ovaries with small antral follicles. Her ovaries reacted slightly to clomiphene citrate therapy; they did not react to the ordinary dose of human menopausal gonadotropin (hMG) (150 IU/day × 9 days), but did react to high-dose hMG (300 IU/day × 6 days) treatment. These ovarian responses to hMG stimulation suggested an FSHR dysfunction of her ovaries. We extracted genomic DNA and analysed FSHR gene sequence after we obtained the written informed consent from the patient under the approval by the Ethics Committee of Yamaguchi Grand Medical Centre and the Yamaguchi University School of Medicine. Direct sequencing revealed a heterozygous mutation 662T−>G resulting in the substitution of valine for glycine at position 221 in exon8 of the FSHR extracellular domain, which was also confirmed by the PCR-RFLP method. The sequencing results also showed two SNPs, 919G−>A (Ala307Thr) and 2039G−>A (Ser680Asn), in exon10. A novel mutation in exon8 of FSHR was identified in a woman with primary amenorrhea whose ovaries reacted to high-dose hMG treatment.