Differences In Number Of Oocytes Research Articles

P-680 Oocyte maturation triggering protocols in in vitro fertilisation treatment: a systematic review and network meta-analysis

Abstract Study question What is the relative effectiveness and safety of final oocyte maturation trigger protocols in women undergoing in vitro fertilisation (IVF) treatment? Summary answer OHSS rate was lowest with GnRH agonist trigger and no difference in LBR was observed comparing various trigger protocols in normal, high and poor responders. What is known already Oocyte maturation trigger prior to oocyte retrieval is a crucial component of ovarian stimulation(OS). Pituitary suppression is an important component of OS in IVF, involving the use of GnRH analogues. Currently, the GnRH antagonist regimen is predominantly used given its comparable efficacy and lower risk of OHSS compared with GnRH agonist (GnRHa) regimens. Whilst only hCG trigger can be used with GnRH agonist regimens, GnRH antagonist regimen enables use of hCG trigger, GnRH agonist trigger or combinations of both as dual or double trigger. However, there is no consensus on how these trigger protocols compare in their effectiveness and safety. Study design, size, duration The following databases were searched until August 2022: MEDLINE, EMBASE, CINAHL, CENTRAL and ClinicalTrials.gov. Randomised controlled trials (RCTs) comparing at least two trigger protocols: hCG trigger, GnRH agonist trigger, dual trigger (hCG and GnRH agonist administered at the same time) and double trigger (GnRH agonist followed by hCG after a time interval) with the antagonist regimen were included. Primary outcome was live birth (LBR) per participant. Secondary outcomes included number of oocytes and OHSS rates. Participants/materials, setting, methods Two reviewers independently screened, selected studies and extracted data. Pairwise and network meta-analyses (NMA) were conducted according to ovarian response groups (normal, high and poor response). Effect estimates were presented as weighted means difference (WMD) and risk ratio (RR) with 95% confidence interval (CI) for continuous and dichotomous outcomes respectively. Quality assessment was performed using GRADE Main results and the role of chance Initial searches identified 4225 studies, of which 54 RCTs involving 5838 women met the inclusion criteria to be included in the analysis. In normal responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.11,95%CI:0.83-1.49;3 studies,430 women,I2=33%,low-certainty evidence, direct comparison(DC)),dual trigger vs hCG(RR:1.14,95%CI:0.99-1.31;4 studies,1007 women,I2=33%,low-certainty evidence, DC),double trigger vs hCG(RR:0.53, 95%CI:0.27-1.06;indirect comparison(IC)),dual vs GnRHa (RR:0.97, 95%CI:0.70-1.34, IC),double vs GnRHa (RR:2.07, 95%CI:0.98-4.38, IC),dual vs double (RR:2.14, 95%CI:1.06-4.32;IC). In high responders, there is no difference in LBR with the GnRHa vs hCG (RR:1.04, 95%CI:0.84-1.29; 3 studies,178 women, I2 = 44%, low-certainty evidence, DC, dual trigger vs hCG (RR:1.82, 95%CI:1.25-2.67; 4 studies,117 women, I2 = 37%, low-certainty evidence, DC), double trigger vs hCG (RR:2.10, 95%CI:1.29-3.43, IC), dual vs GnRHa (RR:0.57, 95%CI:0.37-0.88, IC),double vs GnRHa (RR:0.49,95%CI:0.29-0.88, IC),dual vs double (RR:0.87, 95%CI:0.64-1.18; 1 study,57 women, low-certainty evidence,DC). In poor responders, there may be a difference in LBR when comparing dual trigger to hCG (RR:1.12,95%CI:1.12-2.89 1 study,112 women,low-certainty evidence,DC). OHSS rates were lowest with the use of GnRHa in high responders (RR:0.39,95%CI:0.04-3.78;9 studies;960 women;I2 =43%, low-certainty evidence,DC) and normal responders (RR:0.88, 95%CI:0.78 to 0.99;7 studies; 2246 women; I2=0%, low-certainty evidence,DC). There was no significant difference in number of oocytes or miscarriage risks with the use of any triggers. Limitations, reasons for caution Stratifying results by predicted ovarian response resulted in disconnected networks, limiting our ability to perform NMA for certain groups and outcomes. The certainty of the evidence was limited by high risk of bias. Wider implications of the findings Our results suggest that the use of short GnRH agonist trigger results in reduced OHSS rates in women with predicted normal or high ovarian response. There is no difference in LBR and number of oocytes comparing the different trigger protocols in all response groups (normal, high, poor responders) Trial registration number Not applicable

O-131 BEYOND: a randomised controlled trial comparing efficacy and safety of individualised follitropin delta dosing in GnRH agonist versus antagonist protocols for first ovarian stimulation cycle

Abstract Study question How does a long GnRH agonist versus a GnRH antagonist protocol affect ovarian response when using individualised fixed daily follitropin delta dose for ovarian stimulation? Summary answer BEYOND trial data demonstrates that individualised follitropin delta dosing is safe and effective in a long GnRH agonist protocol in women with AMH ≤35 pmol/L. What is known already Efficacy and safety of a fixed daily dose of follitropin delta, individualised based on bodyweight and anti-Müllerian (AMH), have been established in RCTs using a GnRH antagonist protocol. Preliminary study data shows that individualised follitropin delta is efficacious when used with a long GnRH agonist protocol (RAINBOW trial). There is no comparative data for efficacy and safety of individualised follitropin delta in a long GnRH agonist versus an antagonist protocol. Study design, size, duration This was a randomised, controlled, open-label, multi-centre trial comparing efficacy and safety of individualised follitropin delta dosing in a long GnRH agonist versus an antagonist protocol in participants undergoing their first ovarian stimulation for IVF/ICSI conducted between May 2019 and February 2022. The primary endpoint was the number of oocytes retrieved. Important secondary endpoints included ongoing pregnancy rates and adverse drug reactions, with a special focus on OHSS. A total of 437 participants were randomised. Participants/materials, setting, methods Participants, 18–40 years old with AMH ≤35 pmol/L, were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway and Switzerland. The mean number of oocytes retrieved was compared between the agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. The analyses were based on all randomised subjects, using a multiple imputation method for randomised subjects withdrawing before start of stimulation. Main results and the role of chance Of the 437 randomised subjects, 202 and 204 initiated ovarian stimulation with follitropin delta in the agonist and antagonist groups, respectively. Baseline mean data were: age, 32.3±4.3 years; AMH, 16.6±7.8 pmol/L, respectively. The number of oocytes retrieved was statistically significantly higher in the agonist (11.1±5.9) versus antagonist (9.6±5.5) group, with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, p = 0.0185). The difference in number of oocytes retrieved was influenced by the patients’ age and ovarian reserve, with a greater difference observed in patients <35 years and patients with high ovarian reserve (AMH >15 pmol/L). Cycle cancellations (2.0% versus 3.4%) and transfer cancellations (13.7% versus 14.7%) were similar in both groups. Ongoing pregnancy rate (36.9% vs 29.1%; estimated difference: 7.74% [95% CI: –1.49; 16.97, p = 0.1002]) and other pregnancy outcomes were higher in the agonist versus antagonist protocol group, but the differences were not statistically significant. The most commonly reported adverse events (≥1% in either group) were similar in both groups (headache, OHSS, nausea, pelvic pain or discomfort, and abdominal pain). Incidence of early moderate/severe OHSS was low (1.5% versus 2.5%). Early pregnancy loss was similar between the groups (20% vs 24% of subjects with positive beta-hCG test, respectively). Limitations, reasons for caution Subjects with AMH >35 pmol/L were not enrolled. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/L (greater OHSS risk). OHSS incidence in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Wider implications of the findings In women with AMH ≤35 pmol/L, a fixed daily dose of follitropin delta (individualised according to bodyweight and AMH) showed similar efficacy when used in a long GnRH agonist protocol with no additional safety signals observed and no additional risk of OHSS versus follitropin delta used in an antagonist protocol. Trial registration number ClinicalTrials.gov identifier: NCT03809429; EudraCT number: 2017-002783-40

Controlled Ovarian Stimulation Initiated at Different Phases of the Menstrual Cycle for Fertility Preservation in Oncological Patients: a Retrospective Study.

The purpose of this study is to compare conventional start in early follicular phase (EFP) with late follicular phase (LFP) and luteal phase (LP) in controlled ovarian stimulation (COS) for fertility preservation (FP) to assess differences in clinical outcomes. Retrospective study of the first cycles of COS for FP in oncological patients between 2012 and 2020 in a tertiary hospital. Two-hundred forty-eight cycles were classified into 3 groups: 176 cycles in EFP, 8 cycles in LFP, and 52 cycles in LP. Comparing LFP to EFP, there were no differences in number of oocytes (10.0 [6.3-16.0] vs 12.0 [8.0-18.0]; p = 0.253) or number of metaphase II (MII) obtained (7.0 [2.3-13.3] vs 9.0 [6.0-13.0]; p = 0.229). Total number of days needed was higher in LFP (14.5 [12.5-16.0] vs 3.0 vs 10.0 [8.3-11.0 p = 0.000) but without significant differences in number of days of usage of gonadotropins (11.5 [8.3-12.8] vs 10.0 [8.3-11.0] p = 0.308). No differences were found between LP and EFP in number of oocytes (14.5 [9.0-20.0] p = 0.151) or MII (11.5 [7.0-16.0] p = 0.084). Number of days of gonadotropins (11.0 [10.0-12.0] p = 0.00) and total dosing (3000.0 [2475.0-3600.0] p = 0.013) were significantly higher in LP. FORT and FOI were similar in all groups. COS with a random start in fertility preservation has similar outcomes to EFP start. Therefore, we can initiate COS at any phase of the menstrual cycle with optimal results. However, LP may need more days of stimulation.

Correlation of LH level and steroid concentrations in GnRH antagonist protocol: A sub-analysis of Ganirelix phase III study of China

BackgroundBased on the data obtained from a phase III, multicenter, open-label, randomized clinical trial that compared the use of GnRH agonist vs. antagonist for LH-suppression in IVF cycles, the present study attempted to determine the effect of LH level on steroid concentrations and IVF outcomes in the GnRH antagonist protocol. MethodsA total of 109 patients with the GnRH antagonist protocol were stratified into three subgroups according to the stimulation day six LH levels (LH <25%, 25–75%, and >75%), and the effect of LH on steroid biosynthesis and the related IVF outcomes between subgroups was observed. ResultsIn comparing the three subgroups of GnRH antagonist, no difference in number of oocytes, top quality embryos and ongoing pregnancy was observed. The high LH group on day six was exposed to significantly lower concentrations of rFSH from day six onwards, and had significantly higher estradiol levels on the day of hCG. The progesterone levels did not differ between groups at the start of the stimulation, but patients with the highest LH on day six also had significantly (P < 0.0001) higher progesterone levels on day six (higher estradiol on day six and hCG, lower total rFSH dosage). Due to the significantly lower increase in progesterone in the high LH group between day six and the day of hCG, no difference in progesterone level was observed on the day of hCG. ConclusionsFor steroid biosynthesis, early follicular phase LH levels help pregnenolone metabolize primarily via the ∆5 pathway in the GnRH antagonist stimulation protocol, but not via the ∆4 pathway.

History of cancer and fertility treatment outcomes: a registry linkage study in Massachusetts.

To investigate assisted reproductive technology (ART) outcomes among adolescent and young-adult female cancer survivors. The Society for Assisted Reproductive Technology Clinic Outcome Reporting System (SART CORS) data were linked to the Massachusetts Cancer Registry for 90,928 ART cycles in Massachusetts to women ≥ 18years old from 2004 to 2013. To estimate relative risks (RR) and 95% confidence intervals (CI), we used generalized estimating equations with a log link that accounted for multiple cycles per woman and a priori adjusted for maternal age and cycle year. The main outcomes of interest were ART treatment patterns; number of autologous oocytes retrieved, fertilized, and transferred; and rates of implantation, clinical intrauterine gestation (CIG), live birth, and pregnancy loss. We saw no difference in number of oocytes retrieved (aRR: 0.95 (0.89-1.02)) or proportion of autologous oocytes fertilized (aRR: 0.99 (0.95-1.03)) between autologous cycles with and without a history of cancer; however, cancer survivors required a higher total FSH administered (aRR: 1.12 (1.06-1.19)). Among autologous cycle starts, cycles in women with a history of cancer were less likely to result in CIG compared to no history of cancer (aRR: 0.73 (0.65-0.83)); this relationship was absent from donor cycles (aRR: 1.01 (0.85-1.20)). Once achieving CIG, donor cycles for women with a history of cancer were two times more likely to result in pregnancy loss (aRR: 1.99 (1.26-3.16)). Our analysis suggests that cancer may influence ovarian stimulation response, requiring more FSH and resulting in lower CIG among cycle starts.

Outcomes of ovarian stimulation in the follicular and luteal phases of the menstrual cycle in cancer patients

Objective The purpose of the study was to evaluate the effectiveness of controlled ovarian stimulation in different phases of the menstrual cycle in cancer patients seeking for the preservation of reproductive material before gonadotoxic therapy. Methods A total of 140 patients with oncological diseases underwent ovarian stimulation in the standard protocol with GnRH antagonists in the follicular phase of the cycle (n = 68) and in the random-start protocol in the luteal phase of the menstrual cycle without prescribing GnRH antagonists (n = 72). Results All patients included in the study were comparable in age and AMH level. There were no differences in the mean number of oocytes retrieved in the follicular phase group, and luteal phase group. Similarly, no significant differences were observed in the number of M II oocytes. Conclusions The results of the study demonstrate the equal effectiveness of stimulation protocols in different phases of the menstrual cycle, which allows us to develop a personalized approach to the implementation of reproductive function both in cancer patients and in the routine practice of ART.

P–325 The impact of letrozole on endometrial thickness in IVF cycles

Abstract Study question Does daily administration of letrozole during IVF stimulation affect endometrial thickness ? Summary answer Patients treated with letrozole during fresh IVF cycles had a thinner endometrium on the day of trigger compared to patients who did not receive letrozole. What is known already Letrozole supplementation is commonly used during fertility preservation for breast cancer patients to reduce peak estrogen levels with no adverse effects on embryo outcomes. Studies in poor responders have found that letrozole use resulted in a shorter duration of stimulation and a lower total dose of gonadotropin, with no detrimental effect on IVF outcomes. In normal responders, studies have shown an increase in blastocysts obtained, but have not yet shown an increase in clinical pregnancy rates. There is concern that when a fresh embryo transfer is planned letrozole use may negatively affect endometrial thickness and subsequently diminish pregnancy rates. Study design, size, duration In a retrospective cohort study between January 2009 and June 2019 at a single academic fertility center, we compared the endometrial thickness in 97 cancer patients who underwent IVF-fertility preservation with daily letrozole use to 158 cancer patients who underwent IVF-fertility preservation without letrozole. Participants/materials, setting, methods All women diagnosed with cancer were referred for fertility preservation prior to gonadotoxic treatment exposure and were less than 40 years old at the time of oocyte retrieval. All patients who received letrozole started on day one of stimulation and continued until the day of oocyte retrieval. The primary outcome was endometrial thickness on the day of trigger. The secondary outcomes were number of oocytes retrieved, number of MII retrieved, and maximal estradiol level. Main results and the role of chance During the study period, 336 cancer patients underwent fertility preservation. Eighty-one patients were excluded; 50 because they had an intrauterine device or were on long term oral contraceptives and 31 because endometrial thickness was not documented. Of the remaining 255 patients, 86 had breast cancer, 95 had a hematological cancer and 74 had various other cancers. Ninety-seven cancer patients treated with letrozole were compared to 158 cancer patients who did not receive letrozole. Patients who received letrozole were significantly older (34 vs 28yrs, P &amp;lt; 0.0001). There were no significant differences in baseline characteristics such as BMI, AFC nor in the total duration for stimulation. Endometrial thickness on the day of trigger was significantly less in letrozole treated patients (8 vs 9mm, P &amp;lt; 0.003). There were no significant differences in total number of oocytes retrieved (12.5 vs 11, P = 0.126) nor in the number of mature oocytes (8 vs 8, P = 0.312). Patients in the letrozole group received a higher total gonadotropin dose (2680IU vs 1980IU, P = 0.016). The maximum estradiol level was significantly lower in patients treated with letrozole (1068 vs 3838ml/dl, P = &amp;lt;0.0001). A regression analysis showed that using letrozole during stimulation decreased the endometrial thickness by 0.81mm (CI –1.37 to –0.253, P = 0.005). Limitations, reasons for caution The retrospective nature of this study could have introduced selection and misinformation bias. We report on cancer patients where all oocytes or embryos were vitrified. Without fresh embryo transfer data, it is unclear if a thinner endometrium due to letrozole will effect the implantation or pregnancy rate. Wider implications of the findings: As the use of letrozole expands beyond cancer patients and poor responders, it is important to understand the impact on the endometrium. This study shows that letrozole reduces endometrial thickness. However, the effect on endometrial function remains unknown. Further study is needed before letrozole can be used with fresh transfers. Trial registration number 2020–6370

Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: alternative versus standard stimulation protocols

to evaluate the effectiveness of ovarian stimulation with tamoxifen or letrozole compared to standard ovarian stimulation on the number of oocytes retrieved in women with breast cancer in the course of fertility preservation. Multi-center randomized open-label trial in the Netherlands and Belgium. Women between 18 and 43 years with breast cancer who opted for banking of oocytes or embryos in the course of fertility preservation were included. We randomly assigned them to one of the three study groups; group 1 ovarian stimulation plus tamoxifen (60 mg per day), group 2 ovarian stimulation plus letrozole (5 mg per day) or group 3 standard ovarian stimulation without additional medication. Primary outcome was the number of oocytes retrieved at follicle aspiration. Secondary outcomes were number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. Between January 2014 and December 2018, we randomised 162 women with breast cancer. We analysed the primary outcome for 148 (91%) women of which 142 women (88%) underwent ovum pick up. Mean age of the women was 32 years.51 women underwent ovarian stimulation plus tamoxifen, 51 plus letrozole and 46 standard ovarian stimulation without additional medication. The mean number of oocytes retrieved at follicle aspiration was 12.6 (group 1), versus 14.2 (group 2) versus 13.3 (group 3) (mean difference in number of oocytes: group 1 vs. group 3 -0.675 ;95% CI, -5.6 to 4.3; group 2 vs. group 3 0.871; 95% CI, -4.1 to 5.9). The mean number of oocytes banked was 10.4 (group 1) versus 10.5 (group 2) versus 10.2 (group 3) (mean difference in number of oocytes banked: group 1 vs. group 3 0.243; 95% CI,-4.2 to 4.7; group 2 vs. group 3 0.297; 95% CI, -4.2 to 4.8). Mean number of embryos banked was 5.9 (group 1) versus 4.9 (group 2) versus 5.0 (group 3) (mean difference in number of embryos banked: group 1 vs. group 3 0.857; 95% CI, -3.0 to 4.7; group 2 vs. group 3 -1.33; 95% CI, -4.0 to 3.7). These results show that the addition of tamoxifen or letrozole to standard ovarian stimulation did not effect the number of oocytes or embryos banked in the course of fertility preservation for women with breast cancer. Whether the addition of tamoxifen or letrozole to standard ovarian stimulation affects the long-term follow up in terms of safety in women with breast cancer, remains to be seen.

Ovarian response and follow-up outcomes in women diagnosed with cancer having fertility preservation: Comparison of random start and early follicular phase stimulation - cohort study

ObjectivesTo determine response to controlled ovarian stimulation in a random start cycle and utilisation of cryopreserved oocytes and embryos in cancer patients. Study DesignA retrospective cohort study was carried out in an assisted reproductive treatment centre. Participants included 137 cancer patients who underwent controlled ovarian stimulation for fertility preservation between 1 Feb 2003 and 30 June 2016. The primary outcome variable was number of oocytes retrieved. Multivariable logistic regression analysis was performed, and differences compared using Chi squared test and student t-test as appropriate. P < 0.05 was considered statistically significant. ResultsUsing the antagonist protocol, there was no difference in number of oocytes retrieved between the early follicular phase or at random start stimulation; 11.9 (95% CI 10.3–13.5) and 12.9 (95% CI 9.6–16.2), P = 0.602, respectively. Similarly, the number of embryos frozen was comparable between those starting stimulation in early follicular and random phase, 6.7 (95% CI 5.7–7.7) and 5.1 (95% CI 3.6–6.5), P= 0.1508 respectively. Among patients undergoing fertility preservation, those who returned to attempt a pregnancy had an ongoing pregnancy rate of 24.3%. Overall, 65% of oocytes and embryos were still in storage, however, 16 (11.7%) had elected to have their oocytes or embryos disposed of. Conclusion(s)For women faced with potential gonadotoxic treatment and requiring urgent fertility preservation, ovarian stimulation with the antagonist protocol can be started at random without compromising ovarian response. Pregnancy rates following utilisation of frozen-thawed oocytes and embryos are promising, however, more research is needed to understand reasons underlying disposition of oocytes and embryos especially when survival following cancer treatment has improved significantly.

Intent to treat analysis reveals significantly improved clinical outcomes with aneuploidy testing in an age-matched population

Preimplantation genetic testing for aneuploidy (PGT-A) has been proposed as an improved embryo selection strategy to decrease pregnancy loss and increase live birth rates for infertility patients undergoing in vitro fertilization (IVF). In an intent to treat analysis, we investigated clinical outcomes with PGT-A, compared to patients who have freeze-all blastocyst cycles with embryo selection based on morphology alone. Prospective cohort age-matched study. Infertility couples were identified during their IVF consult as intent to treat with either a freeze-all blastocyst cycle or IVF with PGT-A. Female patients were maternally age-matched between the two treatment groups (mean 32.5 ±3.7 years; n=46 per group). For the ‘Freeze All’ group, blastocysts were vitrified using the Cryotop method on either day 5 (D5) or day 6 (D6) of development. In contrast, for the ‘PGT-A’ group, prior to vitrification, D5 or D6 blastocysts were biopsied and analyzed for chromosome numeration using the VeriSeq™ platform (Illumina). Standard protocols for a hormone replacement frozen embryo transfer (FET) were utilized, with either blastocyst morphology alone (Freeze All) or euploid (PGT-A) embryo selection. Primary outcomes measured included implantation (fetal heart tone), ongoing clinical pregnancy, miscarriage, and live birth rates. Statistical analysis included Student’s t-test and Fisher’s exact test where appropriate, significance at P<0.05. In each treatment group, 46 retrievals were performed with no significant differences in number of oocytes retrieved, fertilized or number of usable blastocysts between the two treatment groups (P≥0.05; ns). Two retrievals (4.4%) resulted in no fertilization and four (8.7%) with no blastocyst development in the Freeze All group, while one (2.2%) resulted in no fertilization and four (8.7%) with no blastocyst development in the PGT-A group (P≥0.05; ns). Additionally, following PGT-A, two (4.4%) cycles ended with all aneuploid blastocysts. Remaining patients underwent FET with significant clinical improvements for primary outcomes measured in the PGT-A group (P<0.05; Table 1). From the prospective of intent to treat analysis, at the time a clinical decision is made to proceed with IVF therapy, the inclusion of PGT-A resulted in significantly improved clinical outcomes in a younger maternally age-matched population. This data reflects that embryo selection incorporating PGT-A should be considered for infertility patients undergoing IVF.Table 1FET OutcomesFreeze All (n=40)PGT-A (n=39)Implantation Rate (fetal heart tone)48.2%78.9%*Ongoing Clinical Pregnancy Rate60%84.6%*Miscarriage Rate16.7%6.1%Live Birth Rate per FET50%79.5%*Live Birth Rate per Intent to Treat43.5%65.2%**P<0.05 Open table in a new tab

Does growth hormone supplementation improve oocyte yield and pregnancy outcome in patients with poor ovarian reserve undergoing in vitro fertilization: A prospective randomized trial

Context: Poor ovarian reserve (POR) results in poor ovarian response to controlled ovarian stimulation (COS) in in vitro fertilization (IVF) cycles. Despite various strategies, clinical pregnancy rates (PRs) remain low in patients with POR. Aims: This study aims to assess if growth hormone (GH) supplementation in POR patients improves oocyte yield and PR in IVF-intracytoplasmic sperm injection (ICSI) cycles. Settings and Design: Prospective, randomized controlled study. Materials and Methods: Patients with anti-mullerian hormone ≤1.1 (ng/ml) and total antral follicle count ≤6 undergoing IVF-ICSI were enrolled in the study. Gonadotropin (GT) stimulation with GT-releasing hormone antagonist protocol was used for IVF. Patients were randomly divided into two groups: group A (n = 30) received recombinant GH 4 IU from the day of COS till the day of human chorionic gonadotropin trigger. Group B (n = 32) received COS and no GH. Statistical Analysis Used: The unpaired t-test and Mann–Whitney test was used. Categorical variables were analyzed using either the Chi-square test or Fisher's exact test. Results: Total dose of GT injections used were significantly less in GH group (Group A) compared to no GH group (Group B) (3000.89 ± 742.20), P = 0.009). There was no statistically significant difference in number of oocytes retrieved (OR), total days of stimulation, mean estradiol levels on the day of trigger and fertilization rates between the two groups. There was a nonsignificant increase in the clinical PR and chemical PR in the GH group. Conclusions: GH cotreatment with antagonist protocol decreased the amount of GTs required for COS but did not improve the oocytes yield, fertilization or PR significantly in POR patients.

Gonadotropin Releasing Hormone Agonists or Antagonists for Preimplantation Genetic Diagnosis (PGD)? A Prospective Randomised Trial.

The use of GnRH analogue medication is essential in reproductive medicine to avoid premature ovulation by pituitary suppression for the duration of ovarian stimulation by gonadotrophins. The type of pituitary suppression by either GnRH agonist analogues versus GnRH antagonist analogues may result in different embryological hence clinical results. Preimplantation genetic diagnosis is a subtype of IVF in which embryos are created for genetic diagnosis of hereditary disorders in order to avoid genetically affected children. Embryological quality hence ovarian stimulation in preimplantation genetic diagnosis is crucial as genetic selection will reduce the number of available embryos to a fraction of the total. The aim of this study was to assess the efficiency of GnRH antagonist versus GnRH agonist treatment for pituitary suppression in ovarian stimulation for PGD, by proxy of number and quality of embryos at cleavage stage available for biopsy. We conducted a prospective randomised controlled trial comparing pituitary suppression by GnRH antagonist versus GnRH agonist in ovarian stimulation for PGD. The primary outcome measure was the number of embryos of sufficient quality for biopsy at cleavage stage. Secondary outcome parameters were the number of blastocysts available of top quality, and clinical pregnancy rate. There was no difference in number of oocytes retrieved, embryos at cleavage stage available for biopsy or embryo quality. The clinical pregnancy rate was higher in the GnRH agonist group; however the sample size was insufficient to allow conclusions. The use of GnRH agonist versus antagonist treatment does not result in differences in a number of oocytes, embryos or embryo quality in ovarian stimulation for preimplantation genetic diagnosis.

Descarga de la maduración final ovocitaria con gonadotropina coriónica humana o un agonista de la GnRH en donantes de ovocitos : análisis retrospectivo de cohortes

El protocolo de antagonistas de la GnRH (antGnRH) ha permitido el uso del agonista de la GnRH (aGnRH) como inductor de la descarga ovulatoria (DO), en reemplazo de la gonadotropina coriónica humana (hCG). Una ventaja importante con respecto al uso del aGnRH en la DO es que disminuye significativamente el riesgo del síndrome de hiperestimulación ovárica (SHEO), debido a su efecto luteolítico, de importancia en casos de donantes de ovocitos. Objetivos: Comparar la proporción de ovocitos obtenidos, calidad ovocitaria/embrionaria, resultado reproductivo y la incidencia de SHEO en ciclos de donación de ovocitos consecutivos, donde la DO fue con hCG o aGnRH. Adicionalmente, se comparó los ciclos con diagnóstico genético preimplantacional. Diseño: Estudio retrospectivo de cohortes. Institución: Grupo PRANOR, Clínica Concebir, Lima, Perú. Participantes: Donantes y receptoras de ovocitos. Intervenciones: Se utilizó un protocolo antGnRH en 43 donantes de ovocitos para 203 ciclos de estimulación consecutiva y DO con hCG (n=127) o aGnRH (n=76) basados en una decisión clínica y del conteo folicular. Los ovocitos fueron asignados, parte de ellos, a un banco de ovocitos vitrificación) o a 303 ciclos de receptoras de ovocitos. Principales medidas de resultados: Ovocitos aspirados, tasa de fecundación, calidad embrionaria, formación a blastocisto. Resultados: Se observó diferencias significativas en el número de ovocitos aspirados a favor del grupo aGnRH sobre el grupo hCG (24,09±12,24 versus 18,69±8,93, p=0,002, respectivamente). No hubo diferencias significativas en el resultado global de proporción de ovocitos maduros, tasa de fecundación, calidad embrionaria, formación a blastocisto entre los grupos comparados. La proporción de embriones cromosómicamente normales fueron similares entre los grupos aGnRH (35,2%) y hCG (34,53%), mientras que las tasas globales de embarazo (64,49% versus 62,59%), implantación (45,41% versus 42,38%) y aborto (8,7% versus 8,7%) fueron comparables. La incidencia de SHEO fue reducida significativamente en el grupo de DO con aGnRH (0%), en comparación al grupo hCG (18,9%, p&lt;0,0001). Conclusiones: La DO con el aGnRH es un método seguro y eficaz para ser aplicado en pacientes con alto riesgo de SHEO, como las donantes de ovocitos, eliminando por completo el SHEO. La calidad embrionaria y resultados reproductivos fueron idénticos entre los grupos de DO con aGnRH y hCG.

Does methotrexate administration for ectopic pregnancy after in vitro fertilization impact ovarian reserve or ovarian responsiveness?

To evaluate the effects of methotrexate (MTX) on the future fertility of women undergoing IVF by comparing ovarian reserve and ovarian responsiveness in the IVF cycle before and after an ectopic pregnancy (EP) treated with MTX. Retrospective cohort study. Private reproductive endocrinology and infertility practice. Sixty-six women undergoing IVF before and after receiving MTX for an EP. Methotrexate administration and ovarian stimulation. Markers of ovarian reserve (day 3 FSH, antral follicle count), measures of ovarian responsiveness (duration of stimulation, peak E2 level, total dose of gonadotropins, number of oocytes retrieved, fertilization rate), and time from MTX administration to subsequent IVF cycle. There were no differences after MTX administration in body mass index (BMI), FSH, or antral follicle count. A greater dose of gonadotropins was used in the cycle after MTX, but there were no differences in numbers of oocytes retrieved or high quality embryos transferred. As expected, there was a slight increase in age in the subsequent IVF cycle. The pregnancy rates (PR) were comparable to the average PRs within the practice when combining all age groups. Methotrexate remains the first line of therapy for medical management of asymptomatic EP and does not compromise ovarian reserve, ovarian responsiveness, or IVF success in subsequent cycles.

Circulating concentrations of leptin, ovarian follicle number, and oocyte lipid content and active mitochondria, in Zebu crossbred cows maintained on standard or improved nutrition

Zebu (Bos indicus) crossbred beef cows (Droughtmaster) were maintained long-term (16 months) on standard nutrition (SN) or improved nutrition (IN). Cows on IN had better body condition and greater (P<0.05) circulating concentrations of leptin than cows on SN (0.7±0.1n/ml and 1.7±0.1n/ml, respectively). There were no outstanding differences between SN and IN cows in basal number of ovarian follicles (≤4mm, 5–8mm, and ≥9mm) and there were also no differences in number of oocytes recovered by oocyte pick-up. Cows on IN had a greater (P<0.05) number of total follicles after stimulation with FSH than cows on SN. Oocytes from cows on IN had greater (P<0.05) lipid content than cows on SN (−0.23±0.16 and 0.20±0.18 arbitrary units, respectively) and oocytes of the former cows also tended to have more active mitochondria, although this was not significant. Cows on IN showed a positive relationship (R2=0.31, P<0.05) between plasma leptin and oocyte lipid content. Lipids are utilized by oocytes during high energy consumptive processes including fertilization and early cleavage. The greater lipid content of oocytes from IN cows could therefore confer a reproductive advantage. The present study has shown relationships between nutrition, body condition, circulating leptin, and oocyte lipid content, but a clear cause-and-effect requires further investigation in the cow.

Response to ovarian stimulation in patients facing gonadotoxic therapy

Chemotherapy naïve patients undergoing embryo/oocyte banking for fertility preservation (FP) were assessed for response to ovarian stimulation. Fifty FP patients facing gonadotoxic therapy were matched by age, race, cycle number, date of stimulation and fertilization method to patients undergoing IVF for infertility or oocyte donation. There were no differences in baseline FSH, anti-Müllerian hormone, antral follicle count and total gonadotrophin dose. FP patients had more immature oocytes (2.2 versus 1.1; P=0.03) and lower fertilization rates per oocyte retrieved (52% versus 70%; P=0.002). There were no differences in numbers of oocytes retrieved, mature oocytes or fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses (3077IU versus 2259IU; P=0.0477) and had more immature oocytes (3.4 versus 1.2; P=0.03) than matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. Overall, chemotherapy naïve FP patients had similar ovarian reserve, response to stimulation and oocyte and embryo yield compared to controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole.With improvement in cancer survival rates, there has been a shift in attention toward management of long-term consequences of cancer therapy, including infertility. Many young women with cancer, particularly those who will be treated with chemotherapy, pursue fertility preservation (FP) strategies for the purpose of banking oocytes or embryos for future use. We examined patients with no prior exposure to chemotherapy who underwent IVF to freeze embryos or oocytes for FP. Fifty FP patients were identified and matched to healthy controls by age, race, cycle number, date of stimulation and fertilization method. There were no differences in baseline measures of ovarian reserve or amount of medication needed to stimulate the ovaries. FP patients had more immature oocytes and lower fertilization rates than controls. There were no differences in number of oocytes retrieved, number of mature oocytes, rate of maturity or number of fertilized embryos. Subgroup analysis revealed that FP patients taking letrozole required higher gonadotrophin doses and had more immature oocytes compared with matched controls. There were no differences in gonadotrophin dose or oocyte immaturity among FP patients not taking letrozole. We demonstrated that FP patients not previously exposed to chemotherapy have similar ovarian reserve, response to stimulation and oocyte and embryo yield compared with infertile and donor controls. Patients who received letrozole required higher gonadotrophin doses and produced more immature oocytes, suggesting that response to ovarian stimulation may be impaired in patients with hormone-sensitive cancers receiving letrozole.

Effects of Ration on Growth and Reproductive Investment from Larva to Sexual Maturity in the Female Cyprinid Minnow, Tanichthys albonubes

AbstractSomatic growth and reproductive investment in female Tanichthys albonubes (Cyprinidae) individually cultured at the laboratory from larva to sexual maturity were examined under low, medium, and satiation food rations. All the 72‐day post‐hatch fish reached sexual maturity under all rations. The standard length, wet body mass, dry ovarian mass, dry liver mass, condition factor, energy content, and number of vitellogenic oocytes were all increased with ration levels. However, food conversion efficiency decreased with ration. There were no significant differences in total number of oocytes per female between rations. The species is a continuous batch‐spawner. The size‐frequency distributions of oocyte diameters showed a continuous pattern, ranging from 0.03 to 0.70 mm, at different rations. The proportion of energy intake allocated to growth decreased with ration levels. Only 3.29–4.60% of energy intake was stored in the ovary. These biological and energetic characteristics allow this fish to reach first maturity with low food intake, although it produced fewer vitellogenic oocytes at lower rations. This property enables T. albonubes survive in its native habitats where food is not only scarce, but also variable temporally and spatially. (© 2011 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

Developmental Programming: Differential Effects of Prenatal Testosterone and Dihydrotestosterone on Follicular Recruitment, Depletion of Follicular Reserve, and Ovarian Morphology in Sheep1

Prenatal testosterone excess programs an array of adult reproductive disorders including luteinizing hormone excess, functional hyperandrogenism, neuroendocrine defects, polycystic ovarian morphology, and corpus luteum dysfunction, culminating in early reproductive failure. Polycystic ovarian morphology originates from enhanced follicular recruitment and follicular persistence. We tested to determine whether prenatal testosterone treatment, by its androgenic actions, enhances follicular recruitment, causes early depletion of follicular reserve, and disrupts the ovarian architecture. Pregnant sheep were given twice-weekly injections of testosterone or dihydrotestosterone (DHT), a nonaromatizable androgen, from Days 30 to 90 of gestation. Ovaries were obtained from Day-90 and Day-140 fetuses, and from 10-mo-old females during a synchronized follicular phase (n = 5-9 per treatment). Stereological techniques were used to quantify changes in ovarian follicle/germ cell populations. Results revealed no differences in numbers of oocytes and follicles between the three groups on Fetal Day 90. Greater numbers of early growing follicles were found in prenatal testosterone- and DHT-treated fetuses on Day 140. Increased numbers of growing follicles and reduced numbers of primordial follicles were found in 10-mo-old, prenatal testosterone-treated females, but not in those treated with DHT. Antral follicles of prenatal testosterone-treated females, but not those treated with DHT, manifested several abnormalities, which included the appearance of hemorrhagic and luteinized follicles and abnormal early antrum formation. Both treatment groups showed morphological differences in the rete ovarii. These findings suggest that increased follicular recruitment and morphologic changes in the rete ovarii of prenatal testosterone-treated females are facilitated by androgenic programming, but that postpubertal follicular growth, antral follicular disruptions, and follicular depletion largely occur through estrogenic programming.

Women with cancer undergoing IVF for fertility preservation: A case-control study of response to exogenous gonadotropins

9582 Background: Early detection programs and advancements in treatment allow women with cancer to live longer lives making quality of life issues, such as preserving fertility important. Review of the male literature has shown that malignancy adversely affects fertility, even prior to the initiation of cancer treatment. Whether the presence of cancer in female patients affects ovarian response to gonadotropin hyperstimulation has not been examined. The objective of this study was to determine if women with cancer, pre-treatment, show a decreased response to ovarian hyperstimulation. We originally presented data on the first 17 patients; this abstract represents an update incorporating a total of 28 women with cancer. Methods: From 2001 to 2006, 28 patients diagnosed with cancer presented seeking fertility preservation. Prior to fertility treatment, day 2 estradiol and FSH levels were assessed. 27 of the patients were hyperstimulated with GnRH antagonist protocols; 1 patient received leuprolide down-regulation prior to hyperstimulation. HCG injection was administered when the lead follicle(s) were ≥ 17 mm and oocyte retrieval was performed 36 hours later. Serum estradiol levels were assessed on the day of hCG administration. Oocytes were harvested in routine fashion and all mature eggs were either cryopreserved as unfertilized gametes or fertilized. Results: The mean age of the cancer patients was 34 ± 5 (20 - 41) years. Serum estradiol levels on the day of hCG administration for cancer patients, 1515 +712 pg/ml was lower than those noted in controls 1852 + 021 pg/ml; p< 0.05. There was no difference in number of oocytes retrieved when comparing all cancer patients to all controls (14 + 9, and 14 + 7, respectively), but younger cancer patients had more (18 ± 9) oocytes retrieved than the older study counterpart (11 ± 9; p=0.03). Conclusions: Cancer patients produce a similar number of oocytes following ovarian hyperstimulation when compared to age-matched infertile controls suggesting that malignancy, itself, does not adversely affect ovarian reserve. However, estradiol levels were significantly lower in women with malignancy. In addition, similar to the general IVF population, age appears to be the primary determinant of oocyte quantity in cancer patients. No significant financial relationships to disclose.

Clinical efficacy of highly purified urinary FSH versus recombinant FSH in volunteers undergoing controlled ovarian stimulation for in vitro fertilization: a randomized, multicenter, investigator-blind trial

To compare the efficacy of highly purified human urinary follicle stimulating hormone (HP-hFSH) versus human recombinant follitropin-alpha (rFSH) in volunteers undergoing controlled ovarian stimulation for IVF. A randomized, controlled, investigator-blind trial. Four assisted reproductive technology centers. One hundred fifty-two IVF patients. Volunteers, aged 18-39, were randomized to HP-hFSH (n = 76) versus rFSH (n = 76) at a starting dose of 300 IU in down-regulated cycles. Number of oocytes, clinical pregnancy rate, and live birth rate with HP-hFSH versus rFSH. The total IU of gonadotropin used did not differ between the two groups. There was no difference in number of oocytes retrieved with HP-hFSH (mean = 16.3) compared with rFSH (mean = 17.1), confidence interval (CI) of difference = -3.79 to +2.18. Clinical pregnancy rate, as defined by the presence of a gestational sac, was 48.7% (CI = 37.0%-60.4%) with HP-hFSH versus 44.7% (CI = 33.3%-56.6%) with rFSH (CI of difference = -11.9% to +19.8%). Live birth rate was 38.2% (29 of 76) in both groups (CI = 27.2%-50.0%), for a difference between groups of 0.0% (CI of the difference = -15.4% to +15.4%). There were no statistically significant differences in mean oocyte number, clinical pregnancy rate, or live birth rate between HP-hFSH versus rFSH.