Ovulation Induction Cycles Research Articles

Clinical Observation of 242 Cases of Polycystic Ovary Syndrome

Objective: To compare the clinical effect and safety between letrozole (LE) and clomiphene citrate (CC) stimulated cycles in women with polycystic ovary syndrome (PCOS). To evaluate the effectivenesses and benefits of letrozole for ovulation induction in infertile women with PCOS. Methods: We retrospectively analyze the clinical data of 242 cases of the first ovulation induction cycle patients with PCOS, who referred to the Department of Reproductive Medicine, The First Affiliated Hospital of Yangtze University from June 2016 to June 2018, and were randomly divided into letrozole group and control group. The experimental group received Letrozole 2.5 mg/d for 5 days during days 3 - 7 of menstrual cycle. The control group was given clomiphene citrate 100 mg/d for 5 days during days 3 - 7 of menstrual cycle. Progynova will be used when the follicular diameter is 14 mm. Results: Letrozole group had less mature follicles, lower estrogen levels, thicker endometrium and higher ovulation rate in HCG day. But there is no difference between two groups in clinical pregnancy rate, single pregnancy rate, abortion rate, prenatal pregnancy delivery and newborns. Conclusion: Letrozole and clomiphene citrate have similar effect on ovulation induction, but we still need a lot of clinical data of letrozole about the safety of follicle, embryo, fetus and newborns.

Effect of oral Tadalafil on endometrial thickness in patients receiving Clomiphene citrate for ovulation induction

Abstract Background Adequate and optimum endometrial development is required for a successful pregnancy to occur. Clomiphene citrate is well known for its negative impact on endometrial thickness. The long-acting phosphodiesterase 5 inhibitor, Tadalafil, was shown to improve endometrial growth in patients under Clomiphene citrate stimulation. Objective To study the effect of Tadalafil on the endometrial thickness in Clomiphene citrate stimulated cycles as compared to clomiphene citrate alone and human menopausal gonadotropins. Study design A randomized controlled study. Setting was at the infertility clinic of Cytogenetic and Endoscopy Unit, Zagazig University Hospital. Material and methods The study included 236 patients who underwent a single cycle of ovulation induction and timed intercourse. Patients were divided into 3 groups: Controlled ovarian stimulation was done in group A by Clomiphene Citrate alone, in group B by Clomiphene Citrate with addition of Tadalafil and in group C by Human Menopausal Gonadotropins. Results As regard the number of cases who got pregnant, we found that there was a statistically significant difference (P Conclusion This study showed that the pregnancy rate achieved with Clomiphene citrate/Tadalafil combination was comparable to that achieved by Human Menopausal Gonadotropins and significantly higher than with Clomiphene citrate alone. This was attributed to the improvement of endometrial thickness by Tadalafil in Clomiphene citrate stimulated patients.

Cost-effectiveness of gonadotrophins compared to clomiphene citrate in anovulatory women who had not conceived after six ovulatory cycles with clomiphene citrate

To compare the costs and effects of six cycles of ovulation induction (OI) with gonadotrophins (FSH) or clomiphene citrate (CC) with or without intra-uterine insemination (IUI) in anovulatory women who already had six ovulatory cycles after CC without conceiving.

Efficacy of patient self-administered recombinant human chorionic gonadotropin (RHCG) is comparable to nurse administred RHCG in ovulation induction cycles

Infertility treatment requires patients to overcome a variety of physical, emotional, and financial obstacles. Often, patients express anxiety over self-administration of medications, including subcutaneous recombinant hCG (rHCG). Midluteal rise in progesterone (P4) levels to >3ng/dL suggest evidence of ovulation, and of ≥9ng/dL of adequate luteinization. Many patients express concern over whether they will adequately be able to self-administer medication. The study sought to determine if the rate and adequacy of ovulatory response is comparable whether a patient or a nurse administers the medication.

Cost effectiveness comparison of frozen thawed blastocyst stage embryo transfer in ovulation induction (letrozole), natural and down-regulated hormone replacement cycles: a propensity score matched study

Frozen embryo transfer (FET) is increasingly employed in the field of assisted reproduction. Different regimens are used to prepare the endometrium including natural cycles (NC), ovulation induction (OI) and hormone replacement cycles (HRT). The cost associated with each regimen may affect decision making. The aim of this study was to identify the most cost-effective procedure in patients undergoing frozen blastocyst transfer

Vitamin D deficiency is associated with poor reproductive outcomes in PCOS but not unexplained infertility

The impact of vitamin D deficiency on the success of ovulation induction (OI) cycles and the risk pregnancy complications after OI has not been extensively investigated. The goal of this study was to evaluate the relationship between preconception vitamin D status and reproductive outcomes in women with a diagnosis of either PCOS or unexplained infertility treated with OI.

Cycle regimens for frozen-thawed embryo transfer.

Cycle regimens for frozen-thawed embryo transfer.

Pregnancy after endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination cycles-a randomized controlled trial.

To study the effect of endometrial scratching in infertile couples undergoing ovulation induction and intrauterine insemination (IUI) cycles. A prospective randomized controlled trial was conducted in the Department of Obstetrics and Gynaecology, AIIMS, New Delhi, India. One hundred forty-four women with primary/secondary infertility were recruited. Couples were either unexplained or male factor infertility. Subjects were randomized into intervention (scratching) and control group. All patients received ovulation induction with clomiphene citrate (day 2-6) 50mg/day +75IU HMG on days 6 and 7. In addition, endometrial scratching was done on day 8 of ovulation induction cycle in intervention group. All couples were planned for three cycles of ovulation induction and IUI over 6months. After each failed cycle, couple was advised to try for natural conception for one cycle. Those who conceived were excluded from further analysis. Primary outcome was clinical pregnancy rate. Secondary outcome measures included conception rate, ongoing pregnancy, abortion and ectopic rate. Baseline characteristics were comparable in both groups. Clinical pregnancy rate was significantly higher in intervention group (31.9%; 23/72) as compared to control group (16.7%; 12/72) (p value 0.030). On per cycle analysis, first IUI cycle had significantly high pregnancy rate (18.1%; 13/72) as compared to control group (5.6%; 4/72). Three patients in intervention group and one in control group conceived in wash out cycle. Ongoing pregnancy rate was significantly higher in scratching group (30.0%; 21/70) as compared to control group (15.7%; 11/70) (p value0.044). Endometrial scratching can be used as a low cost-effective tool to improve clinical pregnancy and ongoing pregnancy rate in IUI cycles. Further large number studies are required to document its role in improving live birth rate. CTRI/2015/12/006419.

A randomized trial of local endometrial injury during ovulation induction cycles.

To investigate the effect of endometrial injury on pregnancy outcomes among infertile women taking clomifene citrate. A prospective randomized trial was undertaken at an Egyptian hospital between January 26, 2015, and July 17, 2016. Eligible women (≥1year primary/secondary/unexplained infertility, aged 20-35years, day-2 follicle-stimulating hormone <12IU/L, normal prolactin/thyroid function/uterine cavity, ≥1 patent tube, male partner with normal semen count and motility, 3 cycles of clomifene citrate without success) were randomly allocated (1:1) using computer-generated numbers into intervention (received endometrial injury on cycle day 15-24) or control groups (sham procedure). Women began ovulation induction on days 3-5 of the following cycle. Participants and investigators were not masked to group assignment. The primary outcomes were clinical pregnancy, spontaneous abortion, and multiple pregnancy rates. Women who completed follow-up were included in analyses. The intervention group included 52 women and the control group 53 women. The clinical pregnancy rate was significantly higher in the intervention group (37% [n=19]) than in the control group (13% [n=7]; P=0.006). No differences between the intervention and control groups were noted for spontaneous abortion rate (11% [2/19] vs 29% [2/7]; P=0.287) or multiple pregnancy rate (11% [2/19] vs 14% [1/7]; P=0.790). No adverse effects were reported. Endometrial injury before ovulation induction could improve chances of pregnancy and its outcomes. CLINICALTRIALS.GOV: NCT02345837.

Interactive case-based learning improves resident knowledge and confidence in reproductive endocrinology and infertility

Resident physicians’ scores on the REI section of the CREOG exam are traditionally low, and nearly 40% of house staff nation-wide perceive their REI knowledge to be poor. We aimed to assess whether an interactive case-based group-learning curriculum would narrow the REI knowledge gap by improving understanding and retention of core REI concepts under the time constraints affecting residents. A three-hour case-based workshop was developed to address four primary CREOG objectives. A multiple-choice test was administered immediately before and after the intervention and 7 weeks post-workshop, to evaluate both knowledge and confidence. Following the intervention, residents self-reported increased confidence with counseling and treatment of PCOS, ovulation induction cycle monitoring, counseling and treatment of POI, and breaking bad news related to infertility (p < 0.05). The multiple-choice exam was re-administered 7 weeks post-intervention, and scores remained significantly improved compared to pre-workshop scores (p < 0.05). At that time, all residents either strongly agreed (91.7%) or agreed (8.3%) that the case-based interactive format was preferable to traditional lecture-based teaching. In conclusion, a nontraditional curriculum aimed at teaching core REI concepts to residents through interactive case-based learning can be successfully integrated into a residency curriculum, and significantly improves knowledge and confidence of critical concepts in REI.

The Relations Between HSG Proven Tubal Occlusion, Stimulated Intrauterine Insemination and Pregnancy Rate.

Background:Tubal factor infertility is one of the main causes of female infertility. Although its sensitivity is low, hysterosalpingography (HSG) is remains the first-line method for evaluating tubal patency.Aims:To compare pregnancy rates in patients with HSG proven proximal or distal unilateral tubal occlusion, and unexplained infertility undergoing both controlled ovarian stimulation (COS) and intrauterine insemination (IUI).Study Design:Case control study.Methods:In total, 237 patients undergoing ovulation induction (OI) with gonadotropins and IUI were divided into two groups and evaluated. Study group consisted 59 patients with HSG proven unilateral tubal pathology, and 178 patients with unexplained infertility taken as control subjects. Cumulative pregnancy rate was the primary endpoint.Results:Cumulative pregnancy rates after three cycles of OI and IUI were 15.25% in study group and 20.79% in control group. Pregnancy rates between two groups were not statistically significant. Although, pregnancy rates in patients with proximal tubal occlusion (21.8%) were higher than in those with distal tubal occlusion (7.4%), the difference was not statistically significant.Conclusion:Our study data shows that, regardless of the HCG proven occlusion area, COS and IUI might be a preferred treatment modality in patient with unilateral tubal occlusion.

Individualised gonadotrophin ovulation induction in women with normogonadotrophic anovulatory infertility: A prospective, observational study

ObjectiveThe aim of this study was to evaluate an individualised gonadotrophin starting dose regimen for women with anovulatory infertility. Study designWe included 71 normogonadotrophic anovulatory infertile women in a prospective, observational study. All underwent one ovulation induction cycle in a flexible, low-dose step-up protocol. The gonadotrophin starting dose (75–150IU/day) was individualised according to a nomogram incorporating menstrual cycle pattern (oligo- or amenorrhoea), BMI, and mean ovarian volume. The number of women who fulfilled the criteria for human chorionic gonadotrophin (hCG) administration (one follicle ≥17mm or 2–3 follicles ≥15mm) was assessed. ResultsOf the 50 women (70.4%) who fulfilled the hCG criteria and underwent intrauterine insemination, 34 (47.9%) achieved monofollicular growth and 16 (22.5%) developed 2–3 mature follicles. Seventeen (23.9%) cycles were converted to in vitro fertilisation (IVF) due to the development of >3 mature follicles, and one (1.4%) cycle was cancelled due to risk of ovarian hyperstimulation syndrome. Baseline total antral follicle count was found to be significantly associated with fulfillment of the hCG criteria (OR 0.96, 95% CI: 0.92–0.99, P=0.01). ConclusionsThe nomogram-based dose regimen was not considered suitable for ovulation induction due to a tendency to overestimate the gonadotrophin starting dose. However, the model may serve as a mild IVF regimen, especially in women prone to excessive follicle growth.

The Effect of Coasting on Intracytoplasmic Sperm Injection Outcome in Antagonist and Agonist Cycle.

Coasting can reduce the ovarian hyperstimulation syndrome (OHSS) risk in ovulation induction cycles before intracytoplasmic sperm injection (ICSI). This study aimed to investigate the effect of gonadotropin-releasing hormone (GnRH) agonist and GnRH antagonist protocols to controlled ovarian hyperstimulation (COH) cycles with coasting on the parameters of ICSI cycles and the outcome. In a retrospective cohort study, 117 ICSI cycles were per- formed and coasting was applied due to hyperresponse, between 2006 and 2011. The ICSI outcomes after coasting were then compared between the GnRH agonist group (n=91) and the GnRH antagonist group (n=26). The duration of induction and the total consumption of gonadotropins were found to be similar. Estradiol (E2) levels on human chorionic gonadotropin (hCG) day were found higher in the agonist group. Coasting days were similar when the two groups were compared. The number of mature oocytes and the fertilization rates were similar in both groups; however, the number of grade 1 (G1) embryos and the number of transferred embryos were higher in the agonist group. Implantation rates were significantly higher in the antagonist group compared to the agonist group. Pregnancy rates/embryo transfer rates were higher in the antagonist group; however, this difference was not statistically significant (32.8% for agonist group vs. 39.1% for antagonist group, P>0.05). The present study showed that applying GnRH-agonist and GnRH-antago- nist protocols to coasted cycles did not result in any differences in cycle parameters and clinical pregnancy rates.

Optimal follicular size for ovulatory trigger in natural and clomiphene citrate intrauterine insemination cycles

Intrauterine insemination (IUI) during a natural cycle (NC) or following ovulation induction with clomiphene citrate (CC) forms the mainstay of fertility treatment in many young patients. IUIs in such patients are frequently performed after administration of a human chorionic gonadotropin (hCG) ovulatory trigger. The primary objective of this study is to identify the optimal lead follicular size for an ovulatory trigger in either NC or CC IUI cycles. Retrospective cohort study. Patients <40 years of age, with patent fallopian tubes, a normal uterine cavity, and a male partner with >15 million sperm/mL, undergoing an IUI in either a NC or CC ovulation induction cycle between 2004 and 2013 were analyzed for inclusion. All patients with a spontaneous LH surge or undergoing successive IUIs in the same treatment cycle were excluded. The hCG ovulatory trigger was administered either subcutaneously or intramuscularly, after visualization of a >17 mm follicle in the NC group or >19 mm follicle in the CC group, and an endometrial thickness of >7 mm in both groups. IUIs were performed 24-30 hours following the ovulatory trigger. Clinical pregnancy rates were plotted for the NC and CC groups against lead follicular size, in increments of 1 mm beginning at 17 mm. Odds ratios (OR) for clinical pregnancy at different lead follicular sizes were calculated by using 17 mm and 19 mm as reference values for the NC and CC groups, respectively. 3272 IUI cycles met inclusion criteria: 1201 NC and 2071 CC. The median age in the NC and CC groups was 36.4 (31.4-41.4) years and 34.3 (29.8-38.8) years, respectively. In the NC group, the clinical pregnancy rate (14%) was highest when the ovulatory trigger was administered at a lead follicular size of 19 mm compared to the reference group of 17 mm (8%). However, these odds were not statistically significant (OR 1.80, 95% CI 0.73-4.41). The aforementioned odds remained unchanged even after adjusting for age. In contrast, the clinical pregnancy rate in the CC group was highest when the lead follicular size was 22 mm at the time of the ovulatory trigger (16%). Compared to the reference group of 19 mm, the odds for clinical pregnancy with a lead follicle of 22 mm was 2.14 times higher (OR 2.14, 95% CI 1.20-3.83; P=0.01). The higher odds for clinical pregnancy persisted even after stratifying for age: 25-35 years (OR 2.55, 95% CI 1.25-5.20) and 35-40 years (OR 1.90, 95% CI 1.01-3.58). Our results suggest that administration of a hCG ovulatory trigger at a lead follicular size of 22 mm is associated with higher odds of clinical pregnancy in patients undergoing IUI following ovulation induction with CC. Although triggering at a lead follicular size of 19 mm in the NC group is also associated with an increased odds of clinical pregnancy, these odds remain non-significant when compared to the reference group of 17 mm.

Pregnancy rate after endometrial scratching in couples with unexplained infertility in ovulation induction & IUI cycles- a randomised controlled trial

Pregnancy rate after endometrial scratching in couples with unexplained infertility in ovulation induction & IUI cycles- a randomised controlled trial

A modified natural cycle results in higher live birth rate in vitrified-thawed embryo transfer for women with regular menstruation

ABSTRACTThere is no consensus regimen for the optimal endometrial preparation for cryopreservation and vitrified-thawed embryo transfer cycles. This is largely caused by the lack of sufficient investigation and analyses on the respective pregnancy and perinatal outcomes by different regimens. This study aimed to compare both pregnancy and perinatal outcomes between the modified natural and artificial cycles in vitrified-thawed day three embryo transfer for women with regular menstruation. A total of 1,482 vitrified-thawed day three embryo transfer cycles were reviewed including 427 modified natural cycles (NC), 132 ovulation induction cycles (OC), 794 artificial cycles (AC), and 129 GnRH agonist artificial cycles (GAC). The primary outcome that was evaluated was live birth rate. The NC regimen demonstrated a higher rate of ongoing pregnancy (43.8% vs. 30.2%, P = 0.002) and a lower rate of late abortion (2.8% vs. 14.0%, P = 0.003) than the GAC regimen as well as a higher implantation rate (31.9% vs. 27.1%, P = 0.008) and live birth rate (43.1% vs. 34.1%, P = 0.002) than the AC regimen. A significantly higher peak endometrial thickness before transfer was observed in patients using the NC and GAC regimens (10.0 ± 1.7, 9.9 ± 2.4) compared to the AC regimens (9.2 ± 1.5, P = 0.000). Multivariate logistic regression showed that the NC protocol was associated with a higher live birth rate. There were no significant differences in rates of pregnancy complications, neonatal mortality, birth defects, mean birth weight, and other perinatal outcomes among the regimens. Modified natural cycle endometrial preparation regimen for vitrified-thawed day three embryo transfer is associated with superior live birth pregnancy outcomes compared to artificial cycles. Future studies are warranted to investigate the underlying biologic mechanisms of these findings.Abbreviations ART: assisted reproductive technology; BMI: body mass index; FET: frozen-thawed embryo transfer; HCG: human chorionic gonadotropin; IVF: in-vitro fertilization; IVF-ET: in-vitro fertilization and embryo transfer; OHSS: ovarian hyperstimulation syndrome; RCTs: randomized controlled trials

Primary Ovarian Carcinoma Associated with Ovulation Induction: A Case Report

Introduction: The relationship between ovulation induction and ovarian cancer is an important issue in gynecology. Case Presentation: The studied patient was a 32-year-old G1P1 woman with abdominal pain who was diagnosed with a large ovarian cyst during ovulation induction, which could possibly raise the risk of ovarian torsion. She had a 2-year secondary infertility and had received three cycles of ovulation induction with letrozole 6 months earlier. An emergency laparoscopy showed large complex ovarian cysts without torsion. We then performed a cystectomy. Based on the pathology report revealing a primary ovarian cystadenocarcinoma, the patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and retroperitoneal lymphadenectomy. Conclusions: The emergence of a suspected ovarian cyst during letrozole-induced ovulation is of great importance and needs to be investigated.

Ovulation Induction is a More Effective Stimulant on Antiovarian Antibody Production than In Vitro Fertilization.

Our aim in this study is to evaluate the effects of in vitro fertilization (IVF), including controlled ovarian hyperstimulation (COH) and the number of oocyte pick-up (OPU) procedures on the development of anti-ovarian antibodies (AOA). To evaluate the effects of IVF procedures, namely, COH and OPU, serum samples for measuring AOA concentration levels by enzyme-linked immunosorbent assay were collected on the third day of the menstrual cycle, at the end of the COH, and after OPU. The AOA levels in IVF patients were significantly higher than the fertile control groups'. In the IVF group, neither COH nor OPU caused any increase in AOA levels when compared to the basal results. AOA levels were higher in patients with a history of 5-8 cycles of ovulation induction, before IVF treatment. There was no relationship between the basal AOA concentrations and the type of infertility, the etiology of infertility or the pregnancy outcomes, whereas there was a relationship between the AOA and the duration of infertility. AOA levels of IVF patients were found to be higher than the fertile control groups'. AOA was found to be related to infertility in patients who had a longer duration of infertility and repeated ovulation induction procedures without IVF. COH and OPU during an IVF cycle did not cause an increase in AOA levels.

Pipelle for Pregnancy (PIP): study protocols for three randomised controlled trials.

BackgroundThe success rate of infertility treatments remains modest. Endometrial injury has been suggested as an intervention to increase the probability of pregnancy in women undergoing assisted reproductive technologies such as in vitro fertilisation (IVF). The majority of studies and systematic reviews have reported that endometrial injury improves the outcomes of IVF, intrauterine insemination and natural conception; however, the size and quality of the studies are poor. The low quality of the available evidence questions the presence of any real beneficial effect, and the applicability of the intervention in different populations remains unclear.Methods/designThe PIP trials are three multi-centre, randomised controlled trials designed to test three separate hypotheses: whether endometrial injury increases the probability of live birth in women or couples1) who are undergoing autologous embryo transfer as part of an IVF cycle (PIP-IVF),2) with unexplained infertility who are attempting to conceive naturally (PIP-UE) and3) with subfertility related to polycystic ovarian syndrome (PCOS) who are on ovulation induction medication and attempting to conceive (PIP-PCOS).Participants will be randomised to either undergo endometrial injury by endometrial pipelle biopsy or to:• no intervention (PIP-IVF), or• a sham procedure (PIP-PCOS and PIP-UE).In PIP-IVF, endometrial injury will be carried out between day three of the cycle prior to the IVF cycle, and day three of the IVF cycle. In PIP-UE and PIP-PCOS, endometrial injury or a sham procedure will be undertaken between days 1–12 of a menstrual cycle or ovulation induction cycle respectively. Participants in PIP-UE and PIP-PCOS will then be followed for three cycles during which time they will attempt to conceive from sexual intercourse. To ensure allocation concealment, randomisation will be carried out using a web-based system or sequentially numbered, opaque, sealed envelopes. The primary outcome is live birth. Secondary outcomes include ongoing pregnancy, clinical pregnancy and miscarriage.The required sample sizes for the PIP studies have been estimated at 840 (PIP-IVF), 350 (PIP-UE) and 280 (PIP-PCOS). Primary analysis will be as per intention-to-treat principles.DiscussionThe PIP trials are designed to address the gaps in the utility of endometrial scratching as a treatment for subfertility in three different populations. If the beneficial effect of this intervention can be confirmed in these settings, endometrial scratching will provide a cost-effective method for helping women and couples to conceive.Trial registrationsPIP-IVF ACTRN12614000626662 registered 13/6/2014; PIP-PCOS ACTRN12614000657628 registered 24/6/2014; PIP-UE ACTRN12614000656639 registered 24/6/2014. The trials are ongoing.

From Infertility to Induced Abortion: A Case of Bilateral Ovarian Dermoid Cysts

Background: A mature teratoma, or dermoid cyst, is the most common ovarian tumor, accounting for 10%–20% of all ovarian tumours and occurs bilaterally in 10%–15% of cases. These cysts are known to occur in patients at any age, but the peak incidence is reported in reproductive age. The issue of infertility is controversial with respect to bilateral ovarian dermoid cysts. Pregnancy is not impossible if there is some healthy ovarian tissue even in one side after surgery for bilateral ovarian dermoid cysts. Case: A 38-year-old woman presented with primary infertility for 4 years. On examination and detailed investigation, she was found to have bilateral ovarian dermoid cysts. Right-sided oophorectomy and a left-sided ovarian cystectomy were performed, preserving healthy ovarian tissue. She conceived during the third cycle of ovulation induction. Results: The outcome was a term healthy baby, delivered by Cesarean section. Eight months postdelivery, she conceived again spontaneously. After repeated counseling to continue the pregnancy, medical abortion was done as per her request. Conclusions: In women with bilateral ovarian dermoid cysts, if future fertility is required, then preservation of some healthy ovarian tissue, even on one side, at the time of surgery can save the fertility of these women. (J GYNECOL SURG 32:129)