Follicle flushing does not improve live birth and increases procedure time: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To determine whether follicle flushing during oocyte retrieval improves live birth or secondary outcomes in assisted reproductive technology (ART). DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women undergoing ART using autologous gametes. INTERVENTION(S): A systematic search of PubMed, EMBASE, Cochrane Database, and Web of Science for randomized controlled trials comparing follicle flushing to direct aspiration during oocyte retrieval published in English between 1989 to 2020. MAIN OUTCOME MEASURE(S): Live birth as primary outcome, and clinical and ongoing pregnancy, total and mature metaphase II (MII) oocytes retrieved, and operating time as secondary outcomes. RESULT(S): Eleven studies were included totaling 1,178 cases. No difference in live birth was demonstrated between follicle flushing and direct aspiration. Clinical pregnancy and ongoing pregnancy were not improved with flushing. Total oocyte and MII yield were lower with flushing compared with direct aspiration. Procedure time was increased with flushing by 2 minutes in poor responders and 9 minutes in normal responders. Other sensitivity analyses did not demonstrate any changes, except the difference in MII yield was no longer statistically significant. CONCLUSION(S): Follicle flushing during oocyte retrieval increases procedure time and does not improve live birth or secondary ART outcomes. Randomized data do not support the use of follicle flushing as an intervention in ART.

Effect and Relationship of Seasons on the High Risk of Ovarian Hyperstimulation Syndrome After Oocyte Retrieval in Patients With Polycystic Ovary Syndrome.

Objective: To investigate the effect of seasons on the incidence of high risk of ovarian hyperstimulation syndrome (OHSS) after in oocyte retrieval in patients with polycystic ovarian syndrome (PCOS) and to establish a nomogram to predict the risk of OHSS. Design: Single-center, retrospective study. Setting: University-affiliated reproductive medicine center. Patients: A total of 2,030 infertility patients with PCOS underwent the follicular phase long-acting long protocol IVF/ICSI in the reproductive medicine center from January 2017 to December 2019. Interventions: None. Main outcome measures: Logistic regression analysis was used to analyze the factors associated with a high risk of OHSS. We established a nomogram to predict the risk of OHSS in infertility patients with PCOS after oocyte retrieval. Results: The incidence of patients at high risk of OHSS was significantly different from season-to-season and was especially higher in the summer and winter. Multivariate logistic analysis showed that gonadotropin dosage, number of retrieved oocytes, estradiol level, average bilateral ovarian diameter on the day human chorionic gonadotropin was administered, type of infertility, and average temperature were independent risk factors for OHSS after oocyte retrieval in PCOS patients. Based on the above independent risk factors, we constructed a prediction model for OHSS risk. To evaluate the efficiency of the prediction model, we calculated the C-index (0.849), area under the receiver operating characteristic curve (0.849), and internal validation C-index (0.846). Decision curve analysis suggested that the prediction model exhibited significant net benefits. Conclusions: The incidence of PCOS patients at high risk for OHSS after oocyte retrieval fluctuated with seasonal temperature changes, and was significantly higher in extreme climates. The prediction model had favorable predictive performance and clinical application value.

Use of fertility preservation services in female reproductive-aged cancer patients.

OBJECTIVE: The objective of the study was to determine the rates and predictors of fertility preservation services among reproductive-aged women with common cancers in the United States. STUDY DESIGN: We used the MarketScan database to identify women 18-45 years of age with lung, breast, colorectal, or cervical cancer who underwent surgery and chemotherapy from 2009 through 2016. Services from 3 months before to 3 months after chemotherapy for evaluation for fertility preservation, laboratory testing for fertility evaluation, and fertility-preserving procedures were captured. Multivariable models were used to assess the factors associated with the use of fertility-preservation services. RESULTS: A total of 18,781 women, including 386 cervical, 1372 colorectal, 246 lung, and 16,777 with breast cancer, were identified. In women 18-35 years old, 11.7% underwent evaluation for fertility preservation, 13.7% underwent laboratory testing, and 6.3% pursued fertility-preserving procedures. The rates of office evaluation, laboratory testing, and performance of procedure were 3.3%, 7.5%, and 1.9 % in women aged 36-40 years and 0.5%, 7.2%, and 0.3% in those aged 41-45 years, respectively. The rate of fertility preservation evaluation rose from 1.0% in 2009 to 5.5% in 2016 (risk ratio, 4.66, 95% confidence interval, 2.38-9.11) while use of fertility-preserving procedures increased from 1.0% to 4.6% (risk ratio, 3.84, 95% confidence interval, 1.94-7.59) during the same time period. In a multivariable model, use of any fertility-preserving interventions were more common in patients with breast cancer (adjusted risk ratio, 2.30, 95% confidence interval, 1.30-4.06), those in the Northeast (adjusted risk ratio, 1.24, 95% confidence interval, 1.10-1.40), and in younger women (18-35 years) (adjusted risk ratio, 2.59, 95% confidence interval, 2.32-2.89). CONCLUSION: Although limited by lack of information regarding cancer stage and desire for future fertility, only a small fraction of reproductive-aged female cancer patients receiving chemotherapy are evaluated in a nationwide sample for fertility preservation or undergo fertility-preserving procedures.

Opioid dispensing patterns after oocyte retrieval.

OBJECTIVE: To study opioid dispensing patterns following oocyte retrieval. DESIGN: Retrospective cohort. SETTING: Not applicable. PATIENT(S): Women undergoing oocyte retrieval with a maximum of 1 opioid prescription in the 12 weeks prior to the procedure, without an opioid use or other substance use disorder. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): We measured the frequency of opioids dispensed within 3 days of oocyte retrieval, most common opioids dispensed; and quantity dispensed, in median (interquartile range [IQR] and 10th-90th percentile ranges) oral morphine milligram equivalents (MME). Multivariate regression analyses were used to calculate odds ratios and 95% confidence intervals (CI) to examine the association between patient characteristics and the occurrence of an opioid dispensing. RESULT(S): In total, 61,463 women with an oocyte retrieval met the criteria for analysis. After oocyte retrieval, 11.9% were dispensed an opioid, most commonly hydrocodone (48.5%), codeine (23.0%), and oxycodone (17.7%). The median (IQR; 10th-90th percentile) oral MME dose dispensed after retrieval was 90 (50-125; 50-207). Women with mood disorders (adjusted odds ratio [aOR] 1.17, 95% CI 1.00-1.36), tobacco use (aOR 1.67, 95% CI 1.18-2.37), or anti-depressant use (aOR 1.62, 95% CI 1.47-1.80) were more likely to fill an opioid prescription, compared to those without these diagnoses. CONCLUSION(S): Although only a small proportion of women fill a prescription for opioids after oocyte retrieval, there is substantial variation in the amount dispensed. Patients with a concurrent mood disorder or those taking anti-depressants were more likely to fill an opioid prescription.

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

BACKGROUND: 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. OBJECTIVE: 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. METHOD: 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. RESULTS: 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. CONCLUSION: 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.

Ovarian reserve and subsequent assisted reproduction outcomes after methotrexate therapy for ectopic pregnancy or pregnancy of unknown location.

OBJECTIVE: To assess ovarian reserve after methotrexate treatment for ectopic pregnancy or pregnancy of unknown location after assisted reproductive technology (ART). DESIGN: Retrospective cohort study. SETTING: Large ART practice. PATIENT(S): Women receiving methotrexate or surgery after ART. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Follicle-stimulating hormone (FSH), antral follicle count (AFC), and oocyte yield compared between women treated with methotrexate or surgery, with secondary outcomes of clinical pregnancy and live birth. RESULT(S): There were 153 patients in the methotrexate group and 36 patients in the surgery group. Neither group demonstrated differences in ovarian reserve or oocyte yield in a comparison of the before and after treatment values. The change in ovarian reserve and oocyte yield after treatment were similar between the two groups. The number of doses of methotrexate was not correlated with changes in ovarian reserve, indicating no dose-dependent effect. Time between treatment and repeat ART was not correlated with outcomes. Live birth in subsequent cycles was similar in the two groups. CONCLUSION(S): Ovarian reserve and subsequent ART cycle outcomes were reassuring after methotrexate or surgical management of ectopic pregnancy. No adverse impact of methotrexate was detected in this large fertility cohort as has been previously described elsewhere.

Progesterone level at oocyte retrieval predicts in vitro fertilization success in a short-antagonist protocol: a prospective cohort study.

OBJECTIVE: To evaluate the distribution of P levels on the day of oocyte retrieval as it relates to pregnancy outcome in an antagonist protocol, which may be at higher risk for elevated P levels. DESIGN: Prospective cohort study. SETTING: Academic IVF center. PATIENT(S): One hundred eighty-six women undergoing controlled ovarian hyperstimulation with an antagonist protocol. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Implantation, pregnancy, and spontaneous abortion rates were collected. RESULT(S): Implantation rate (positive hCG 14 days after ET) and pregnancy rate were significantly higher when the P level was <12 ng/mL on the day of oocyte retrieval. Miscarriage rates were higher when the P level was ≥12 ng/mL, although this did not reach statistical significance. CONCLUSION(S): Elevated P on the day of oocyte retrieval is associated with significantly lower implantation and ongoing pregnancy rates. This is the first study to date to both uncover the distribution of P on the day of oocyte retrieval in an antagonist cycle and determine the impact an elevation may have on pregnancy outcome.

Antimüllerian hormone in gonadotropin releasing-hormone antagonist cycles: prediction of ovarian response and cumulative treatment outcome in good-prognosis patients.

OBJECTIVE: To assess the relationships between serum antimüllerian hormone (AMH) and ovarian response and treatment outcomes in good-prognosis patients undergoing controlled ovarian stimulation using a gonadotropin-releasing hormone (GnRH) antagonist protocol. DESIGN: Secondary analysis of data prospectively collected in a randomized, assessor-blind trial comparing two different gonadotropin preparations with respect to ongoing pregnancy rate. SETTING: Twenty-five centers in seven countries. PATIENT(S): 749 women, aged 21 to 34 years, with primary diagnosis of infertility being unexplained infertility or mild male factor infertility and with serum follicle-stimulating hormone (FSH) level 1-12 IU/L and antral follicle count (AFC) ≥10. INTERVENTION(S): Controlled ovarian stimulation with highly purified human menopausal gonadotropin (hphMG) or recombinant FSH in a GnRH antagonist cycle with compulsory single-blastocyst transfer and potential subsequent 1-year cryopreserved blastocyst replacement in natural cycles. MAIN OUTCOME MEASURE(S): Relationships between AMH at start of stimulation and ovarian response and treatment outcome. RESULT(S): Serum AMH concentration was strongly correlated with oocyte yield: AMH accounted for 85%, FSH for 14%, and inhibin B and AFC for <1% each of the explained variation in oocyte yield. Also, AMH showed a high accuracy for the prediction of poor (≤3 oocytes) and high response (≥15 oocytes), which was statistically significantly better than basal FSH, AFC, or inhibin B. AMH was statistically significantly positively associated with ongoing pregnancy rate in the fresh cycle as well as with the 1-year cumulative ongoing pregnancy and live-birth rates. CONCLUSION(S): There is a positive relationship between AMH and oocyte yield in GnRH antagonist cycles, and AMH is the best predictor for identifying patients with poor and high ovarian response. The positive association between AMH and cumulative live-birth rates after fresh and cryopreserved cycles reflects the availability of more oocytes/blastocysts, not higher quality. CLINICAL TRIAL REGISTRATION NUMBER: NCT00884221.

Oocyte cryopreservation: advances and drawbacks.

The field of oocyte cryopreservation (OC) had advanced dramatically since the first reported birth from cryopreserved oocytes in 1986, with a significant increase in pregnancy rates described over the past 5 years due to improvements in vitrification technology, a cryopreservation method which virtually means to achieve a "glass-like" state through avoidance of ice formation. The potential clinical benefits of achieving efficient OC protocols have long been recognized. Specifically, OC can be offered to women who face fertility-threatening situations such as therapy for cancer or rheumatologic disease, premature ovarian insufficiency, or need for ovarian surgery as a measure to preserve fertility. Moreover, many women who plan to delay childbearing are interested in pursuing OC in order to protect against age-related fertility decline. For infertility practices, efficient OC technology stands to dramatically streamline donor egg programs, and is a helpful adjuvant in situations where sperm is unexpectedly unavailable at the time of egg retrieval and for couples who do not wish to cryopreserve supernumerary embryos created from in vitro fertilization for moral / ethical reasons. This review will describe the history of OC technology over the past three decades, discuss clinical circumstances for its implementation, and address areas where more research is needed. Given the remarkable improvements in pregnancy rates witnessed over the past five years, OC is certain to play a much larger role in reproductive medicine over the coming decades.

[Preservation of fertility in tumour patients]. / Erhaltung der Fertilität bei Tumorerkrankungen.

The success rates of present-day chemotherapy have provoked a rising awareness with regard to the preservation of quality of life among successfully treated patients. Among other factors, quality of life also implies the capacity to procreate. Unfortunately, both in men and women chemotherapy often irreversibly destroys the production of gametes, thereby causing permanent infertility. By its long-standing experience with the cryopreservation of oocytes, zygotes and embryos, reproductive medicine may offer assistance to those patients. Whereas the storage of cryopreserved semen has now become standard in most institutions, the options for the preservation of fertility in women suffering of malignant disease are still limited. Although cryopreservation of non-fertilized oocytes or of pronuclear cells has been established, both the number of oocytes that can be collected within the short time interval between the first detection of the tumour and the initiation of chemotherapy and the modest developmental capacity per frozen/thawed oocyte markedly limit the option of ovarian hyperstimulation and assisted reproduction. Several successful deliveries of healthy infants have now proven the feasibility of ovarian tissue cryopreservation and later orthotopic transplantation after successful tumour therapy. Further refinement of the techniques involved, but also the formation of multidisciplinary networks are expected to offer a solution for young women struck by cancer but striving to survive and to lead a fulfilled life.