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

2018 ◽  
Vol 230 ◽  
pp. 10-14 ◽  
Author(s):  
Charles Muteshi ◽  
Tim Child ◽  
Eric Ohuma ◽  
Muhammad Fatum
Keyword(s):  
Cohort Study ◽  
Fertility Preservation ◽  
Ovarian Response ◽  
Follicular Phase ◽  
Early Follicular Phase

Randomised controlled trial on the effect of clomiphene citrate and gonadotropin dose on ovarian response markers and IVF outcomes in poor responders

2020 ◽  
Author(s):  
R Moffat ◽  
C Hansali ◽  
A Schoetzau ◽  
A Ahler ◽  
U Gobrecht ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Primary Outcome ◽  
Clomiphene Citrate ◽  
Ovarian Response ◽  
Serum Levels ◽  
Follicular Phase ◽  
Poor Responders ◽  
Starting Dose ◽  
Early Follicular Phase ◽  
Randomised Controlled

Abstract STUDY QUESTION Does the gonadotropin (GN) starting dose and the addition of clomiphene citrate (CC) during the early follicular phase influence oocyte yield in poor responders undergoing ovarian stimulation for IVF treatment? SUMMARY ANSWER The number of retrieved oocytes was similar regardless of the starting dose of GN (150 versus 450 IU) with or without the addition of CC (100 mg from Day 3 to 7 versus placebo). WHAT IS KNOWN ALREADY ART in poor responders is a challenge for patients and clinicians. So far, randomised controlled studies addressing interventions have shown that neither the GN dose nor the addition of oral medication has any significant effect on the clinical outcome of ART in poor responders. There is limited knowledge about the effect of GN starting dose in combination with CC during the early follicular phase of ovarian stimulation on ovarian response markers and ART outcome. STUDY DESIGN, SIZE, DURATION This single-centre randomised double-blinded clinical trial was conducted from August 2013 until November 2017. Using the Bologna criteria, 220 of 2288 patients (9.6%) were identified as poor responders and 114 eligible participants underwent ovarian stimulation in a GnRH-antagonist protocol for ART. PARTICIPANTS/MATERIALS, SETTING, METHODS The participants were equally randomised to one of four treatment arms: Group A (n = 28) received 100 mg CC (Day 3–7) and a starting dose of 450 IU HMG, Group B (n = 29) received 100 mg CC and a starting dose of 150 IU HMG, Group C (n = 30) received placebo and a starting dose of 450 IU HMG and Group D (n = 27) received placebo and a starting dose of 150 IU HMG. Serum levels of FSH, LH, estradiol and progesterone were measured on Day 1 and 5 and on the day of ovulation induction. Available embryos were cultured up to the blastocyst stage and were always transferred in the same cycle. The primary outcome was the number of oocytes collected after ovarian stimulation. Other outcome measures were response to ovarian stimulation, embryo development and obstetrical outcome. MAIN RESULTS AND THE ROLE OF CHANCE All study participants (n = 114) fulfilled at least two of the Bologna criteria for poor responders. Median age of the study population was 38.5 years. There were 109 patients who underwent oocyte retrieval. The number of oocytes retrieved was similar among the groups (±SD; 95% confidence intervals); A: 2.85 (±0.48; 2.04–3.98), B: 4.32 (±0.59; 3.31–5.64); C: 3.33 (±0.52; 2.45–4.54); D: 3.22 (±0.51; 2.36–4.41); P overall = 0.246. However, ovarian stimulation with 150 IU plus CC resulted in a higher number of blastocysts compared to ovarian stimulation with 450 IU plus CC (±SD; 95% confidence intervals); A: 0.83 (±0.15; 0.58–1.2), B: 1.77 (±0.21; 1.42–2.22); P overall = 0.006. Mean FSH serum levels were lower in the groups with a starting dose of 150 IU. Adding CC did not affect mean serum FSH levels. There were no differences in estradiol concentrations among the groups. Endometrial thickness was lower in the groups receiving CC. The overall live birth rate (LBR) was 12.3%, and the cumulative LBR was 14.7%. LIMITATIONS, REASONS FOR CAUTION The trial was powered to detect differences in neither the number of blastocysts nor the LBR, which would be the preferable primary outcome of interventional trials in ART. WIDER IMPLICATIONS OF THE FINDINGS We found that ovarian stimulation with 150 IU gonadotrophin in combination with 100 mg CC produced more blastocysts. The effect of adding CC to GN on LBR in poor responders remains to be proven in randomised trials. High GN doses (450 IU) resulted in high FSH serum levels but increased neither the estradiol levels nor the number of retrieved oocytes, implying that granulosa cell function is not improved by high FSH serum levels. Lower starting doses of GN lead to a reduction of costs of medication. The small but significant difference in blastocyst formation and the lower FSH levels in the treatment groups receiving less GN may be an indication of better oocyte quality with higher developmental competence. STUDY FUNDING/COMPETING INTEREST(S) The costs for the HMG used for ovarian stimulation were provided by IBSA Switzerland. The study was also supported by the Repronatal Foundation, Basel, Switzerland. The authors declare no conflict of interest. TRIAL REGISTRATION NUMBER NCT01577472 TRIAL REGISTRATION DATE 13 April 2012 DATE OF FIRST PATIENT’S ENROLMENT August 2013

Studies on the influence of gonadotrophin levels in the early follicular phase on the ovarian response to stimulation

1991 ◽  
Vol 6 (1) ◽  
pp. 113-117 ◽  
Author(s):  
Robert G. Forman ◽  
Jacques Demouzon ◽  
Marie C. Feinstein ◽  
Jacques Testart ◽  
Réné Frydman
Keyword(s):  
Ovarian Response ◽  
Follicular Phase ◽  
Early Follicular Phase

Prenatal diethylstilbestrol exposure and reproductive hormones in premenopausal women

2015 ◽  
Vol 6 (3) ◽  
pp. 208-216 ◽  
Author(s):  
L. A. Wise ◽  
R. Troisi ◽  
E. E. Hatch ◽  
L. J. Titus ◽  
K. J. Rothman ◽  
...  
Keyword(s):  
Repeated Measures ◽  
Premenopausal Women ◽  
Reproductive Hormones ◽  
Follicular Phase ◽  
Inhibin B ◽  
Reproductive Age ◽  
Endogenous Hormones ◽  
Reproductive Disorders ◽  
Early Follicular Phase

Diethylstilbestrol (DES), a synthetic estrogen widely prescribed to pregnant women in the mid-1900s, is a potent endocrine disruptor. Prenatal DES exposure has been associated with reproductive disorders in women, but little is known about its effects on endogenous hormones. We assessed the association between prenatal DES exposure and reproductive hormones among participants from the Harvard Study of Moods and Cycles (HSMC), a longitudinal study of premenopausal women aged 36–45 years from Massachusetts (1995–1999). Prenatal DES exposure was reported at baseline (43 DES exposed and 782 unexposed). Early follicular-phase concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol were measured at baseline and every 6 months during 36 months of follow-up. Inhibin B concentrations were measured through 18 months. We used multivariable logistic and repeated-measures linear regression to estimate odds ratios (OR) and percent differences in mean hormone values (β), respectively, comparing DES exposed with unexposed women, adjusted for potential confounders. DES-exposed women had lower mean concentrations of estradiol (pg/ml) (β=−15.6%, 95% confidence interval (CI): −26.5%, −3.2%) and inhibin B (pg/ml) (β=−20.3%, CI: −35.1%, −2.3%), and higher mean concentrations of FSH (IU/I) (β=12.2%, CI: −1.5%, 27.9%) and LH (IU/I) (β=10.4%, CI: −7.2%, 31.3%), than unexposed women. ORs for the association of DES with maximum FSH>10 IU/I and minimum inhibin B<45 pg/ml – indicators of low ovarian reserve – were 1.90 (CI: 0.86, 4.22) and 4.00 (CI: 0.88–18.1), respectively. Prenatal DES exposure was associated with variation in concentrations of FSH, estradiol and inhibin B among women of late reproductive age.

scholarly journals Optimum Number of Oocytes Retrieved Among Patients With Polycystic Ovary Syndrome Treated Using The Follicular Phase Long-Acting Long Protocol: A Retrospective Cohort Study

2021 ◽  
Author(s):  
Ting Yu ◽  
Di Wu ◽  
Jun Zhai
Keyword(s):  
Cohort Study ◽  
Retrospective Cohort ◽  
Polycystic Ovary ◽  
Ovarian Response ◽  
Follicular Phase ◽  
Optimum Number ◽  
High Quality ◽  
Ovary Syndrome ◽  
Long Acting ◽  
Long Protocol

Abstract Background: The optimum number of oocytes retrieved by the follicular phase long-acting long protocol is still unknown. This study aimed to analyze the optimum oocyte number in patients with polycystic ovary syndrome (PCOS) undergoing this protocol.Methods: A total of 1816 PCOS patients aged <35 years who were undergoing their first cycle of in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) between January 2017 and June 2019 were identified and reviewed. All patients underwent stimulation using a follicular phase long-acting long protocol. In this retrospective cohort study, patients were categorized into seven groups according to the number of oocytes retrieved (group A, 1–5; group B, 6–10; group C, 11–15; group D, 16–20; group E, 21–25; group F, 26–30; group G, >30). The main outcome indicators were the rates of high-quality embryo, fresh cycle pregnancy, cumulative pregnancy, and “freezing all” for high ovarian response. The cumulative pregnancy and “freezing all” rates for high ovarian response were analyzed using multivariate logistic analysis.Results: The high-quality embryo rate decreased with the increase in the number of oocytes retrieved (P<0.001). In the <20 oocyte group, the clinical and cumulative pregnancy rates increased with the number of oocytes retrieved, and the “freezing all” rate for high response was within 30%. In the >20 oocyte group, with an increase in the number of oocytes retrieved, no significant change was found in the clinical and cumulative pregnancy rates (P>0.05); however, the incidence of “freezing all” rate for high response was significantly increased (P<0.001). After correcting for confounding factors, the number of oocytes retrieved was an independent predictor of the “freezing all” rate for high ovarian response (odds ratio [OR], 1.085; 95% confidence interval [CI] 1.057–1.113) and cumulative pregnancy rate (OR 1.091, 95% CI 1.057–1.126). The high-quality embryo rate was significantly affected by the cumulative pregnancy rate (OR, 59.076; 95% CI: 29.591–117.938).Conclusion: In PCOS patients aged <35 years treated using the follicular phase long-acting long protocol, considering clinical outcomes, laboratory indicators, and safety, appropriate ovarian stimulation should be used to control the number of oocytes retrieved at 11–20.

P–455 Breast cancer recurrence in women with and without controlled ovarian stimulation for fertility preservation. Cohort study

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
R Pesce ◽  
A F Vinacur ◽  
V Taboada ◽  
C Allemand ◽  
S Marciano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Neoadjuvant Chemotherapy ◽  
Propensity Score ◽  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Cancer Recurrence ◽  
Metastatic Breast ◽  
Significant Difference

Abstract Study question Do patients diagnosed with breast cancer who undergo ovarian stimulation for fertility preservation prior to chemotherapy have a higher risk of recurrence of the disease? Summary answer There was no statistically significant difference in the hazard ratio for breast cancer recurrence in fertility preservation-stimulated women compared to non-stimulated ones What is known already While many women with early breast cancer benefit from chemotherapy treatments in increasing disease-free survival, they are also at risk of permanent chemotherapy induced ovarian failure. Oocyte cryopreservation with an adapted protocol with letrozole may reduce the possible deleterious effect of the hyper estrogenic state during the controlled ovarian hyperstimulation (COH). Although fertility preservation in women diagnosed with breast cancer seems safe, the follow-up periods of most studies are short in time. In addition, follow-up data of COH before neoadjuvant chemotherapy in women with hormone negative tumor receptors is still scarce and briefly reported. Study design, size, duration It was a retrospective cohort study, where 208 women with non-metastatic breast cancer were included. The recruitment period was from 01/01/2009 to 01/12/2019. The minimum follow-up period was 6 months, and the maximum, 130 months. Participants were divided into two cohorts, those who received controlled ovarian hyperstimulation prior to their cancer treatment and those who did not. Patients were followed until disease recurrence, death, loss to follow-up, or end of the study Participants/materials, setting, methods Setting: university hospital in Buenos Aires, Argentina. We included women aged 18 to 45 years with a recent histological diagnosis of non-metastatic breast cancer who had to receive chemotherapy with gonadal toxicity. We excluded patients with a history of previous chemotherapy or radiotherapy for another cancer disease, or menopause. Follow-up was at least an annual clinical check-up and breast imaging. Cohorts were analysed using a Cox-proportional hazards model, adjusted for propensity score for receiving stimulation. Main results and the role of chance We included 208 women, 39 in the COH group and 169 in the non-stimulated group (NSG). The only statistically significant difference was in age: median years 33.7 (interquartile range -IQR- 30.9 to 36.9) and 40.0 years (IQR 36.8 to 44.0), respectively. The median size of cancer nodules was 19.0 millimetres (IQR 10.0–30.0) and 17.0 (IQR 11.0–25.0), p 0.547; percentage of positive lymph nodes: 41.0% vs 39.3%, p 0.841; positive hormonal receptors: 84.6% vs 85.2%, p 0.925; percentage of neoadjuvant chemotherapy: 20.5% vs 11.4%, p 0.128. There were also no statistically significant differences regarding tumour stage, high Ki–67 labelling index, positive breast cancer genes (BRCA 1 or 2), and radiotherapy. Overall, 18.0% of patients had cancer recurrence in the COH group and 20.7% in the NSG (p 0.699). Crude cancer recurrence rates were similar: 5.96 per 100 patients/year (95%CI 2.84–12.50), and 4.65 per 100 patients/year (95%CI 3.34–6.47), respectively. The crude hazard ratio (HR), comparing the COH group vs the NSG was 1.32 (95%CI 0.58–2.97; p 0.507). The adjusted HR using a propensity score for receiving ovarian stimulation treatment was 1.08 (95%CI 0.39–2.98; p 0.887). Results were similar if adjusted for age, neoadjuvant chemotherapy, and other confounders. Limitations, reasons for caution This was a single-center retrospective cohort study. There might be unknown or residual confounders that could influence results. Nevertheless, we accounted for treatment bias using a propensity score for ovarian stimulation. Results should be extrapolated with caution, especially in other non-university institutions and populations. Wider implications of the findings: This study provides new evidence on the safety of controlled ovarian stimulation in breast cancer patients prior to chemotherapy treatment, in a Latin American population. Letrozole continues to show safety and efficacy as an adapted protocol in breast cancer. Trial registration number Not applicable

P–433 Pregnancy and livebirth after fertility preservation in cancer patients

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
S Arab ◽  
E Suarthana ◽  
W Buckett
Keyword(s):  
Cohort Study ◽  
Cancer Survivors ◽  
Cancer Treatment ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Anti Cancer ◽  
Reproductive Material

Abstract Study question What do we know about pregnancy and livebirth after IVF- fertility preservation treatment in women with cancer? Summary answer Most women conceived spontaneously (60%) and more than 50% of those who returned to use their cryopreserved reproductive material have delivered at least one child. What is known already Diminishing ovarian reserve and declining future reproductive potential are important issues in cancer survivors after anti-cancer treatment exposure. Publications on pregnancy and livebirth after fertility preservation in women with cancer are sparse. Studies report most cancer patient who underwent fertility preservation do not come back and use their frozen reproductive material. The purpose of this study was to investigate the fertility preservation outcome among cancer survivors. Study design, size, duration A retrospective cohort study was conducted at a single academic fertility center from including 336 cancer patients who underwent IVF-fertility preservation from January 2009 to June 2020. Participants/materials, setting, methods We included all women with cancer aged ≤40 years old who were referred for fertility preservation treatment prior to chemotherapy. Primary outcome: Number of pregnancies and livebirths after spontaneous conception and/or using their stored frozen material. Secondary outcomes: We also evaluated the utilization rate of the stored reproductive material and mortality rate among those with follow up data. Main results and the role of chance Of 336 patients who underwent IVF-fertility preservation, 214 (63.69%) elected oocyte cryopreservation, 86 (25.5%) underwent both embryo and oocyte cryopreservation and 36 (10.7`%) underwent embryo cryopreservation. Follow up data were available in 198 (58.9%) patients with a mean follow up of 3.2 years. Of 198, 16 (8%) patients died, 40 (20%) became pregnant. Of those pregnant patients, 24 (60%) became spontaneously pregnant and 16 (40%) became pregnant after frozen oocyte or frozen embryo treatment cycles. Almost a quarter (72.5%) of the pregnancies resulted in livebirths. In total, only 23 (7%) patients had returned for frozen oocyte or frozen embryo treatment cycle, of which 16 (70%) achieved a pregnancy and 10 (63%) achieved at least one live birth. Of 142 patients who were still alive at follow up but did not get pregnant, 51 (39%) were in remission from their cancer but had not chosen to use their stored reproductive material; 44 (31%) were still on anti-cancer treatment and had not started trying yet; 13 (9%) were suffering from the end-stage cancer disease; and 7 (5%) had used their stored reproductive material but failed and stopped trying to get pregnant. Limitations, reasons for caution The main limitation was the retrospective cohort study design which could introduce unidentified selection biases. Wider implications of the findings: Of women who underwent IVF-fertility preservation for cancer, most did not come back for treatment for a variety of reasons. Of those who became pregnant, 60% conceived spontaneously. Of those who used their cryopreserved reproductive material, 63% delivered at least one child. Trial registration number 2021/6935

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