Pregnancy confirmed after controlled ovarian stimulation for infertility: A case report.

RATIONAL: Induction of ovarian stimulation by use of the gonadotropin-releasing hormone agonist (GnRHa) long protocol in the luteal phase is a common practice and results in stable pregnancy and live births; it is often used in patients with normal ovarian function. Some patients with normal ovulation may be pregnant before ovulation induction, which can be easily confirmed by asking the patient about cessation of menstruation. However, some pregnancy complications may cause vaginal bleeding along with normal menstrual blood loss; in such a situation, hormone levels can often mirror that seen in pituitary down-regulation and the value of ß-HCG may be less than 5 mIU/mL. Under these conditions, the physician might start the cycle of ovarian stimulation. During ovarian stimulation, the increase in ß-HCG can cause premature luteinization and follicle maturation disorder, and poor embryo quality, which can easily be overlooked. In this study, we report a case of pregnancy at the end of controlled ovarian stimulation induced by GnRHa long protocol in the luteal phase, followed by follicle maturation disorder and poor embryo quality. This case provided a reference and served as a cautionary note that could perhaps obviate occurrence of similar cases. PATIENT CONCERNS: A 30-year-old woman with a diagnosis of unexplained infertility was scheduled for in vitro fertilization embryo culture (IVF) at our clinic. Pregnancy was confirmed at the end of controlled ovarian stimulation, which was followed by follicular maturation disorder and poor embryo quality. DIAGNOSIS: The patient with a diagnosis of unexplained infertility was scheduled for IVF at our clinic. INTERVENTIONS: Oocyte retrieval was still arranged for her after confirmation of pregnancy. As per the ß-HCG level and the trans-vaginal ultrasound examination findings, we considered 2 possibilities: an adverse intrauterine pregnancy or extra-uterine pregnancy. Therefore, we decided to terminate the pregnancy; hence, 50 mg/d of mifepristone was given for 2 days, combined with 200 µg misoprostol. OUTCOMES: Elevated ß-HCG level had an adverse effect on maturation and fertilization of oocytes, and even embryo quality. CONCLUSION: Once pregnancy is confirmed, ovulation induction should be terminated as soon as possible.

Double daily doses of cetrorelix may raise follicular phase progesterone more compared to single doses in poor ovarian response patients.

PURPOSE: There is evidence that follicular phase progesterone rise [FPPR] adversely affects fresh in vitro fertilization [IVF] cycles. A single daily dose of cetrorelix has been used to prevent early luteinizing Hormone (LH) surge. We speculated that doubling the daily dose might have a positive effect in patients who have early LH surges despite receiving the single daily dose treatment. However, a double daily dose of cetrorelix seems to cause FPPR in poor ovarian response (POR) patients. MATERIALS AND METHODS: On human chorionic gonadotropin [hCG] injection days, the progesterone levels of POR patients who received a single daily dose of cetrorelix (group 1, n = 59) were compared with progesterone levels of the patients who received a double daily dose of cetrorelix (group 2, n = 75). The two groups had statistically similar demographic data. The patients who had FPPR were detected, and a comparison of progesterone levels, using 0.8, 1.0, and 1.2 [ng/mL] of progesterone as cut-off levels, was made between patients of both groups. RESULTS: FPPR patients in group 2 had significantly higher progesterone levels during hCG day, contrary to expectations. When progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 1 patients, 15.3%, 13.6%, and 6.8% of the patients developed FPPR, respectively When the progesterone cut-off levels of 0.8, 1.0, and 1.2 [ng/mL] were used for group 2, the results detected were 45.3%, 30.7%, and 21.3%, respectively. A significant statistical difference in progesterone levels was observed between the groups. CONCLUSION: While the double daily dose of cetrorelix was initially thought to more effectively suppress early LH rise by some authors, we have seen that it increases the FPPR more when compared to a single daily dose regime. We suggest using frozen cycles instead of fresh cycles in order to have better endometrial receptivity in patients who seem to benefit from higher daily doses of cetrorelix.

Optimising Follicular Development, Pituitary Suppression, Triggering and Luteal Phase Support During Assisted Reproductive Technology: A Delphi Consensus.

Background: A Delphi consensus was conducted to evaluate global expert opinions on key aspects of assisted reproductive technology (ART) treatment. Methods: Ten experts plus the Scientific Coordinator discussed and amended statements plus supporting references proposed by the Scientific Coordinator. The statements were distributed via an online survey to 35 experts, who voted on their level of agreement or disagreement with each statement. Consensus was reached if the proportion of participants agreeing or disagreeing with a statement was >66%. Results: Eighteen statements were developed. All statements reached consensus and the most relevant are summarised here. (1) Follicular development and stimulation with gonadotropins (n = 9 statements): Recombinant human follicle stimulating hormone (r-hFSH) alone is sufficient for follicular development in normogonadotropic patients aged <35 years. Oocyte number and live birth rate are strongly correlated; there is a positive linear correlation with cumulative live birth rate. Different r-hFSH preparations have identical polypeptide chains but different glycosylation patterns, affecting the biospecific activity of r-hFSH. r-hFSH plus recombinant human LH (r-hFSH:r-hLH) demonstrates improved pregnancy rates and cost efficacy versus human menopausal gonadotropin (hMG) in patients with severe FSH and LH deficiency. (2) Pituitary suppression (n = 2 statements): Gonadotropin releasing hormone (GnRH) antagonists are associated with lower rates of any grade ovarian hyperstimulation syndrome (OHSS) and cycle cancellation versus GnRH agonists. (3) Final oocyte maturation triggering (n=4 statements): Human chorionic gonadotropin (hCG) represents the gold standard in fresh cycles. The efficacy of hCG triggering for frozen transfers in modified natural cycles is controversial compared with LH peak monitoring. Current evidence supports significantly higher pregnancy rates with hCG + GnRH agonist versus hCG alone, but further evidence is needed. GnRH agonist trigger, in GnRH antagonist protocol, is recommended for final oocyte maturation in women at risk of OHSS. (4) Luteal-phase support (n = 3 statements): Vaginal progesterone therapy represents the gold standard for luteal-phase support. Conclusions: This Delphi consensus provides a real-world clinical perspective on the specific approaches during the key steps of ART treatment from a diverse group of international experts. Additional guidance from clinicians on ART strategies could complement guidelines and policies, and may help to further improve treatment outcomes.

Effects of using letrozole in combination with the GnRH antagonist protocol for patients with poor ovarian response: A meta-analysis.

This meta-analysis aimed to compare the outcomes of the gonadotrophin-releasing hormone (GnRH) antagonist/letrozole protocol with those of the conventional GnRH antagonist protocol for poor responders undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We searched for relevant articles in PubMed, EMBASE, Google Scholar, and retrieved 452 records. Eventually, we selected five eligible trials with data for 564 patients characterized as poor ovarian responders. Our meta-analysis revealed that the clinical pregnancy rate (per cycle) with administration of letrozole might be a higher than that in the control groups (risk rate [RR]: 1.57, 95% confidence interval [CI]: 1.00-2.44, p = 0.05). .Moreover,it indicated that the total dose of gonadotrophin was significantly decreased with the administration of letrozole compared to control groups(mean difference [MD]: -529.37, 95% CI: -1207.45 to -111.25, p = 0.001),.However, there was no statistical difference in the number of retrieved oocytes(MD: 0.59, 95% CI: -0.36-1.54, p = 0.22), cycle cancelation rate (RR: 0.81, 95% CI: 0.58-1.12, p = 0.20), or estradiol concentration on the day of HCG administration(MD: -28.19, 95% CI: -77.71-21.33, p = 0.26) in the presence or absence of letrozole combination in the GnRH antagonist protocol. In conclusion, letrozole administration might improve clinical pregnancy rate in conventional GnRH antagonist protocol for poor responders. Moreover, letrozole co-treatment aslo can reduce the economic burden of poor responders during the GnRH antagonist cycle. Nevertheless, large-scale and multi-center randomized controlled trials are needed to further evaluate the efficacy of adjunctive letrozole administration in the GnRH antagonist protocol.

Ovarian stimulation for fertility preservation in women with cancer: A systematic review and meta-analysis comparing random and conventional starts.

OBJECTIVE: In female cancer patients anticipating chemotherapy or radiation, oocyte retrieval for fertility should be performed as efficiently as possible to avoid postponing cancer treatments. Our objective was to compare clinical outcomes among female cancer patients who underwent a conventional early follicular phase-start ovarian stimulation cycle and those who underwent a random-start ovarian stimulation cycle. EVIDENCE REVIEW: A systematic review of the literature was performed in accordance with PRISMA guidelines. Medline, Embase.com, Scopus, Cochrane Library, and Clinicaltrials.gov databases were searched to identify all original research published in English through July 2020 on the topic of female cancer patients undergoing ovarian stimulation with a random or conventional start. Studies lacking a comparison group or including women who had already undergone chemotherapy at the time of ovarian stimulation were excluded. The primary author assessed all identified article titles and abstracts, and two independent reviewers assessed full-text articles and extracted data. A meta-analysis with a random-effects model was used to calculate weighted mean differences (WMDs) for outcomes of interest. The primary outcome was the number of mature (meiosis II) oocytes retrieved. Secondary outcomes included duration of stimulation, total dose of gonadotropins, total number of oocytes retrieved, fertilization rate, and number of embryos or zygotes cryopreserved. RESULTS: A total of 446 articles were screened, and 9 full-text articles (all retrospective cohort or prospective observational) were included for review. Additionally, pooled primary retrospective data from two institutions were included. In total, data from 10 studies including 1653 women were reviewed. Five studies reported the number of embryos cryopreserved, and four reported fertilization rates. Random-start cycles were slightly longer (WMD 0.57 days, 95 % confidence interval [CI] 0.0-1.14 days) and used more total gonadotropins (WMD 248.8 international units, 95 % CI 57.24-440.40) than conventional-start cycles. However, there were no differences in number of mature oocytes retrieved (WMD 0.41 oocytes, 95 % CI -0.84-1.66), number of total oocytes retrieved (WMD 0.90 oocytes, 95 % CI -0.21-2.02), fertilization rates (WMD -0.12, 95 % CI -1.22-0.98), or number of embryos cryopreserved (WMD 0.12 embryos, 95 %CI -0.98-1.22) between random-start and conventional-start cycles. All outcomes except for the parameter "total oocytes retrieved" yielded an I2 of over 50 %, indicating substantial heterogeneity between studies. CONCLUSION(S): Although random-start cycles may entail a longer duration of stimulation and use more total gonadotropins than conventional-start cycles, the absolute differences are small and likely do not significantly affect treatment costs. The similar numbers of mature oocytes retrieved, fertilization rates, and number of embryos cryopreserved in the two start-types suggest that they do not differ in any clinically important ways. Given that random-start cycles can be initiated quickly, they may help facilitate fertility preservation for cancer patients.

Defining thresholds for abnormal premature progesterone levels during ovarian stimulation for assisted reproduction technologies.

OBJECTIVE: To evaluate methodologies to establish abnormal progesterone (P) levels on the day of trigger for recommending freeze only cycles. DESIGN: Threshold analysis and cost analysis. SETTING: Private ART practice. PATIENT(S): Fresh autologous ART. INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): Live birth. RESULT(S): Fourteen established statistical methodologies for generating clinical thresholds were evaluated. These methods were applied to 7,608 fresh ART transfer cycles to generate various P thresholds which ranged widely from 0.4 to 3.0 ng/mL. Lower thresholds ranged from 0.4 to 1 ng/mL and classified the majority of cycles as abnormal as well as required very large number needed to treat (NNT) to increase one live birth. Frozen embryo transfer was cost-effective when P was ≥1.5 ng/mL, with 12% of the population having an abnormal test result and an NNT of 13. Statistical and cost-effective thresholds clustered between 1.5 and 2.0 ng/mL. CONCLUSION(S): Statistically significant thresholds for P were demonstrated as low as 0.4 ng/mL but resulted in a very large NNT to increase one live birth. A clinical benefit to a freeze-only approach was demonstrated above P thresholds ranging from 1.5 to 2.0 ng/dL. At these thresholds, elevated P has a demonstrable and clinically significant negative effect and captures a smaller percentage of the patient population at higher risk for fresh transfer failure, thus making freeze-only a cost-effective option.

Role of metformin for ovulation induction in infertile patients with polycystic ovary syndrome (PCOS): a guideline.

Metformin alone compared with placebo increases the ovulation rate in women with polycystic ovary syndrome (PCOS) but should not be used as first-line therapy for anovulation because oral ovulation induction agents such as clomiphene citrate or letrozole alone are much more effective in increasing ovulation, pregnancy, and live-birth rates in women with PCOS. There is fair evidence that metformin alone does not increase rates of miscarriage when stopped at the initiation of pregnancy and insufficient evidence that metformin in combination with other agents used to induce ovulation increases live-birth rates.

Top quality blastocyst formation rates in relation to progesterone levels on the day of oocyte maturation in GnRH antagonist IVF/ICSI cycles.

Cycles with progesterone elevation during controlled ovarian stimulation (COS) for IVF/ICSI are commonly managed with a "freeze-all" strategy, due to a well-recognized detrimental effect of high progesterone levels on endometrial receptivity. However, also a detrimental effect of elevated progesterone on day-3 embryo quality has recently been found with regards to top quality embryo formation rate. Because blastocyst culture and cryopreservation are largely adopted, we deemed relevant to determine whether this detrimental effect is also seen on blastocyst quality on day 5-6. This issue was investigated through a large two-center retrospective study including 986 GnRH antagonist IVF/ICSI cycles and using top quality blastocyst formation rate as the main outcome. Results showed that on multivariate analysis sperm motility (p<0.01) and progesterone levels at ovulation triggering (p = 0.01) were the only two variables that significantly predicted top quality blastocyst formation rate after adjusting for relevant factors including female age, BMI, basal AMH and total dose of FSH used for COS. More specifically, progesterone levels at induction showed an inverse relation with top quality blastocyst formation (correlation coefficient B = -1.08, 95% CI -1.9 to -0.02) and ROC curve analysis identified P level >1.49 ng/ml as the best cut-off for identification of patients at risk for the absence of top quality blastocysts (AUC 0.55, p<0.01). Our study is the first to investigate the top quality blastocyst formation rate in relation to progesterone levels in IVF/ICSI cycles, showing that increasing progesterone is associated with lower rates of top quality blastocyst. Hence, the advantages of prolonging COS to maximize the number of collected oocytes might eventually be hindered by a decrease in top quality blastocysts available for transfer, if increasing progesterone levels are observed. This observation extends the results of two recent studies focused on day-3 embryos and deserves further research.

Impact of endometrial cavity fluid on assisted reproductive technology outcomes.

BACKGROUND: The impact of endometrial cavity fluid (ECF) on assisted reproductive technology (ART) outcomes has not been evaluated in a meta-analysis. OBJECTIVES: To evaluate the impact of ECF on the outcome of ART cycles. SEARCH STRATEGY: PubMed, China Academic Journals Full-text Database, and China Doctoral/Masters Dissertations Full-text Databases were searched for reports published in any language before January 1, 2015, using relevant keywords. SELECTION CRITERIA: Studies were included if they compared the outcome of ART in women with and without ECF. DATA COLLECTION AND ANALYSIS: Background information, participants' characteristics, and study outcomes were recorded. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. MAIN RESULTS: Six studies evaluating 5928 ART cycles were included. The pregnancy rate was significantly lower in the group with ECF than in the group without ECF (OR 0.74, 95% CI 0.55-0.98; P=0.03). The same association was observed if the analysis included only patients with hydrosalpinx (OR 0.36, 95% CI 0.15-0.86; P=0.02). CONCLUSIONS: The clinical pregnancy rate after ART is significantly lower among patients with ECF than among those without ECF. In addition, if ECF is found in patients with hydrosalpinx, ART cycles should be cancelled after oocyte retrieval.

Luteal phase supplementation after gonadotropin-releasing hormone agonist trigger in fresh embryo transfer: the American versus European approaches.

The challenges in attaining an adequate luteal phase after GnRH agonist (GnRHa) trigger to induce final oocyte maturation have resulted in different approaches focused on rescuing the luteal phase insufficiency so that a fresh transfer can be carried out without jeopardizing IVF outcomes. Over the years, two different concepts have emerged: intensive luteal support with aggressive exogenous administration of E2 and P; and low-dose hCG rescue in the form of a small dose of hCG either on the day of oocyte retrieva or on the day of GnRHa trigger (the so called "dual trigger"). Both approaches have been shown to be effective in achieving pregnancy rates similar to those obtained after conventional hCG trigger and resulting in a very low risk of ovarian hyperstimulation syndrome (OHSS). Although the idea of freezing all embryos after GnRHa trigger and transferring them in a subsequent frozen-thawed cycle has been gaining momentum, a fresh transfer leading to the live birth of a healthy child is currently considered to be the goal of IVF treatment.

Adding the phytoestrogen Cimicifugae Racemosae to clomiphene induction cycles with timed intercourse in polycystic ovary syndrome improves cycle outcomes and pregnancy rates - a randomized trial.

BACKGROUND: Owing to their potential to act as estrogen receptor modulators and interfere with aromatase enzyme in animal studies, phytoestrogens (PE) may be useful as part of ovulation induction for polycystic ovary syndrome (PCOS). PATIENTS AND METHODS: Patients <35 years, presenting with infertility and PCOS, were included and randomly allocated to either group I (clomiphene citrate; CC) or group II (CC plus Cimicifugae racemosae; CR). Primary outcome was pregnancy rate. Secondary outcomes included ovulation, midcycle serum estradiol and luteinizing hormone (LH) as well as mid-luteal serum progesterone. RESULTS: Analysis included 98 patients in group I versus 96 patients in group II. Both groups were matched regarding demographics and basic data. Significant differences were elicited when comparing days until HCG injection (15.0 ± 1.7 versus 12.0 ± 1.9, p=0.91), endometrial thickness (mm) (8.5 ± 1.9 versus 12.5 ± 1.9, p<0.001), serum levels of mid-luteal and midcycle estradiol (p<0.001; Figure 2), LH (IU/ml) (p<0.001) as well as mid-luteal progesterone (p<0.001). PE plus CC group had significantly higher clinical pregnancies per cycle (33/192 (17.2%) versus 71/204 (34.8%), p<0.01), compared to the CC only group. CONCLUSIONS: Adding CR to clomiphene-induction cycles with timed intercourse in polycystic ovarian syndrome improves cycle outcomes and pregnancy rates.

Biomarkers of ovarian response: current and future applications.

With our increasing appreciation that simply maximizing oocyte yield for all patients is no longer an appropriate stimulation strategy and that age alone cannot accurately predict ovarian response, there has been an explosion in the literature regarding the utility of biomarkers to predict and individualize treatment strategies. Antral follicle count (AFC) and antimüllerian hormone (AMH) have begun to dominate the clinical scene, and although frequently pitted against each other as alternatives, both may contribute and indeed be synergistic. Their underlying technologies are continuing to develop rapidly and overcome the standardization issues that have limited their development to date. In the context of in vitro fertilization (IVF), their linear relationship with oocyte yield and thereby extremes of ovarian response has led to improved pretreatment patient counseling, individualization of stimulation strategies, increased cost effectiveness, and enhanced safety. This review highlights that although biomarkers of ovarian response started in the IVF clinic, their future extends well beyond the boundaries of assisted reproduction. The automation of AMH and its introduction into the routine repertoire of clinical biochemistry has tremendous potential. A future where primary care physicians, endocrinologists, and oncologists can rapidly assess ovarian dysfunction and the ovarian reserve more accurately than with the current standard of follicle-stimulating hormone (FSH) is an exciting possibility. For women, the ability to know the duration of their own reproductive life span will be empowering and allow them to redefine the meaning of family planning.

[Mexican National Consensus on Assisted Reproduction Treatment]. / Consenso Nacional Mexicano de Reproducción Asistida.

BACKGROUND: It is estimated that 15% of couples living in industrialized countries are infertile, ie have failed to conceive, reproductive age, after 12 months ormore of regular intercourse without contraception. During the past decade has increased the demand for fertility treatments because they believe are moreeffective now. OBJECTIVE: To unify the therapeutic approach and service to patients and set a precedent for a Mexican Official Standard respect and support for the legislation of these procedures. METHOD: Consensus by technical experts group panel with the participation of 34 national centers accredited for use in assisted reproduction. He organized seven workshops with the following themes: 1) selection of patients for assisted reproduction treatment, 2) schemes controlled ovarian stimulation for assisted reproduction techniques of high complexity, 3) preparation and egg retrieval technique, 4) transferembryo; 5) luteal phase supplementation; 6) indications and techniques of cryopreservation and 7) informed consent. Each table had a coordinator who wrote and presented the findings to the full, it made a number of observations until they reached unanimity of criteria, which are reflected in this document. RESULTS: Patient selection for assisted reproduction techniques is the first step of the process. Proper selection lead to success, in the same way that a bad pick up for failure. In the case of egg donation the most important recommendation is that only one to two embryos transferred in order to reduce multiple pregnancy rates and maintaining high pregnancy rates.

High frequency of discordance between antimüllerian hormone and follicle-stimulating hormone levels in serum from estradiol-confirmed days 2 to 4 of the menstrual cycle from 5,354 women in U.S. fertility centers.

OBJECTIVE: To determine the frequency of clinical discordance between antimüllerian hormone (AMH, ng/mL) and follicle-stimulating hormone (FSH, IU/L) by use of cut points defined by response to controlled ovarian stimulation in the same serum samples drawn on estradiol-confirmed, menstrual cycle days 2 to 4. DESIGN: Retrospective analysis. SETTING: Fertility centers in 30 U.S. states and a single reference laboratory with uniform testing protocols. PATIENT(S): 5,354 women, 20 to 45 years of age. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Frequency of discordance between serum AMH and FSH values. RESULT(S): Of the 5,354 women tested, 1 in 5 had discordant AMH and FSH values defined as AMH <0.8 (concerning) with FSH <10 (reassuring) or AMH ≥ 0.8 (reassuring) with FSH ≥ 10 (concerning). Of the women with reassuring FSH values (n = 4,469), the concerning AMH values were found in 1 in 5 women in a highly age-dependent fashion, ranging from 1 in 11 women under 35 years of age to 1 in 3 women above 40 years of age. On the other hand, of the women with reassuring AMH values (n = 3,742), 1 in 18 had concerning FSH values, a frequency that did not vary in a statistically significant fashion by age. CONCLUSION(S): Clinical discordance in serum AMH and FSH values was frequent and age dependent using common clinical cut points, a large patient population, one reference laboratory, and uniform testing methodology. This conclusion is generalizable to women undergoing fertility evaluation, although AMH testing has not been standardized among laboratories, and the cut points presented are specific to the laboratory in this study.

A short narrative review of the feasibility of adopting mild ovarian stimulation for IVF as the current standard of care.

INTRODUCTION: Mild ovarian stimulation has been conceived, proposed and implemented in clinical practice as a safer and cheaper alternative to conventional strategies of controlled ovarian hyperstimulation in preparation for in vitro fertilization (IVF). Our aim was to summarize the key evidence on this topic and explore its possible role as the standard treatment option for women undergoing IVF. MATERIALS AND METHODS: A short narrative review of the existing literature, with emphasis on mild ovarian stimulation clinical and cost effectiveness, as well as treatment limitations. RESULTS: Numerous studies highlight mild ovarian stimulation's favorable characteristics with respect to oocyte/embryo quality, reduced patient risk, and ease of intervention. There is, however, a need for high-quality laboratory environment. Limitations regarding poor responders, older women, or those seeking ovarian stimulation for non-infertility indications should also be considered. Finally, outcomes on the cumulative success rates and the cost effectiveness of mild ovarian stimulation remain inconclusive. CONCLUSION: Mild ovarian stimulation protocols for IVF should currently be implemented only in carefully selected populations. Further research is needed to clarify the remaining controversies in this IVF approach.

The conflict between hierarchical ovarian follicular development and superovulation treatment.

In mammals with a low ovulation rate phenotype, ovarian follicular development is thought to be hierarchical with few, if any, antral follicles at similar stages of development. The hypothesis being tested herein was that if most follicles are in a functionally different state, then the application of exogenous hormones to increase ovulation rate will not overcome the hierarchical nature of follicular development. Using sheep as the experimental model, the functional states of all non-atretic antral follicles > or =2 mm diameter were assessed in individual ewes (N=10/group) during anoestrus with or without pregnant mare's serum gonadotrophin (PMSG) treatment, or after a standard superovulation regimen, or during the follicular phase of the oestrous cycle. The functional states of these follicles were assessed by measuring the FSH- or human chorionic gonadotrophin (hCG)-induced cAMP responses of granulosa cells in vitro. There were significant overall effects across the treatment groups on the responses of granulosa cells to either FSH or LH (both P<0.001). It was concluded that for anoestrous ewes with or without PMSG treatment, and ewes during the follicular phase, granulosa cell populations of many follicles (> or =2 mm diameter) did not share a similar cAMP response to FSH ( approximately 50% of follicles) or hCG (>90% of follicles) either on a per cell or total cell basis. After superovulation, < or =30 and 10% respectively of the granulosa cell populations shared similar responses to FSH and LH with regard to follicular diameter and cAMP output. Thus, exogenous hormone treatments used routinely for increasing oocyte yield do not effectively override the hierarchical pattern of ovarian follicular development during the follicular phase.

Effect of coasting on IVF cycle characteristics and outcome in short vs. long GnRH agonist protocols.

AIMS: To compare the results of IVF cycles following coasting in patients treated with long versus short GnRH agonist protocols. METHODS: A retrospective comparative study in which all women aged 35 years or less attending the IVF unit from 2000 to 2006 in whom coasting was used in GnRH agonist protocols were included. Data on coasting-related variables and outcome were collected from the files and compared between the short GnRH agonist (n = 78) and long GnRH agonist (n = 181) cycles. RESULTS: The short GnRH agonist cycles were characterized by higher E2 levels during coasting and longer duration of coasting than the long GnRH agonist cycles. Although the number of retrieved oocytes was lower following coasting in the short protocol, there was no difference between the groups in fertilization rate, number of high-quality embryos available for transfer, and pregnancy rate. Pregnancy rate in both protocols was negatively correlated to E2 level at initiation of coasting. The overall moderate and severe OHSS rate after coasting was 5.1% in the short-protocol group and 6.0% in the long-protocol group (p = 0.76). CONCLUSIONS: The ovarian response curve to coasting is longer in the short than in the long GnRH-agonist protocol, but there is no significant difference in pregnancy or OHSS rates.

Outcomes of new quality standards of follitropin alfa on ovarian stimulation: meta-analysis of previous studies.

BACKGROUND: Human follicle-stimulating hormone (hFSH; follitropin alfa) can be employed therapeutically to induce ovarian follicular development in assisted reproduction treatments. Current recombinant hFSH (r-hFSH) preparations available for clinical use are labeled either in terms of the bioactivity expressed in international units (IU) or in mass (microg). Several clinical trials have tried to assess the clinical implications of the physicochemical improvements in the dosing of follitropin alfa filled by mass (FbM). The aim of this study was to perform a meta-analysis of previous studies in order to assess the efficacy and safety of ovarian stimulation using follitropin alfa FbM compared with follitropin alfa filled by international units (FbIU). METHODS: A literature search was carried out in scientific databases to find published articles and abstracts comparing both hormone preparations. A fixed effects model meta-analysis was performed. The variables studied include the average dose (IU), days of treatment, estradiol peak, follicles >14 mm, number of extracted oocytes, number of embryos obtained, number of cases of ovarian hyperstimulation syndrome (OHSS), and clinical pregnancies. RESULTS: A total of six studies met the stated criteria and were included in the meta-analysis. In these studies, the average r-hFSH dose per patient was 230.29 IU less with administration of follitropin alfa FbM compared with FbIU, and the number of days of treatment was reduced by 0.48. In addition, a significantly greater number of oocytes (0.84) were extracted, more embryos (0.88) were obtained, and a higher peak level of estradiol (613.08 pmol/L) was achieved in the patients undergoing ovarian stimulation with follitropin alfa FbM. However, no statistically significant differences were observed in the number of follicles >14 mm, clinical pregnancies, or OHSS cases. CONCLUSION: Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.