Spontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin

doi:10.1016/S1472-6483(10)60581-0

Reproductive BioMedicine Online

Volume 16, Issue 2, 2008, Pages 245-249

https://doi.org/10.1016/S1472-6483(10)60581-0 Get rights and content

Abstract

The objective of this retrospective analysis was to evaluate the number of spontaneous ovulations occurring before oocyte retrieval in natural cycle IVF (nIVF) with and without the use of indomethacin. A total of 121 patients who underwent modified nIVF cycle between December 2003 and July 2006 were included in the study; 171 cycles without indomethacin and 84 cycles with indomethacin, started when the leading follicle reached 14 mm in size, were compared. The number of cycles with ovulation before oocyte retrieval and the number of cycles with no oocytes at retrieval were assessed with and without indomethacin. In addition, the pregnancy rates in the two groups of patients were analysed. There were 28 cycles (16%) in which ovulation occurred before oocyte retrieval in the group where no indomethacin was used and five cycles (6%) in which ovulation occurred before retrieval in the group where indomethacin was used. There was a statistically significant association between premature ovulation and indomethacin, with an odds ratio of 3.8 (95% confidence interval, 1.2–12.3). The oocyte retrieval per started cycle was 64% without indomethacin and 76% with indomethacin (P < 0.04). The clinical pregnancy rate per embryo transfer was 14% without indomethacin and 21% with indomethacin (not significant).

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Dr Kadoch completed his studies in medicine at the Saint-Antoine Faculty of Medicine, Université Paris VI, France in 1995. After 5 years of residency in Obstetrics and Gynaecology in Paris, he was offered a fellowship with Professor René Frydman (Clamart–France) where he acquired training in reproductive medicine and surgery. He spent 2 years as a Clinical Fellow in Reproductive Endocrinology and Infertility in the Centre Hospitalier de l'Université de Montréal, and is currently an Assistant

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Cited by (35)

Natural cycle in vitro fertilization (IVF): from the origins of IVF to current healthcare practice
2022, Clinica e Investigacion en Ginecologia y Obstetricia
El principio básico de la fecundación in vitro en ciclo natural (FIV-CN) recae en el reclutamiento mediante la selección folicular espontánea, minimizando la manipulación del ciclo de la mujer. Recientemente esta técnica ha suscitado mayor interés y se han puesto en valor muchas de sus ventajas respecto a la FIV convencional (FIVc). FIV-CN y FIVc son tratamientos complementarios que permiten ampliar el espectro terapéutico en las parejas con indicación de FIV. La FIV-CN constituye un tratamiento a considerar especialmente en la paciente con mal pronóstico para la FIVc por baja reserva ovárica. La edad es su principal factor pronóstico y los resultados son aceptables hasta los 40 años. El principal factor limitante de la FIV-CN es el riesgo de cancelación por ovulación, que puede reducirse mediante diferentes estrategias. No obstante, los resultados por transferencia embrionaria son satisfactorios en diferentes series publicadas.
The basic principle of natural cycle in vitro fertilization (NC-IVF) lies in recruitment through spontaneous follicular selection, avoiding or minimizing the use of drugs and manipulation of the woman's cycle. In recent years, this technique has attracted growing interest and many of its advantages over conventional IVF (cIVF) have been highlighted. NC-IVF and cIVF should be considered complementary treatments, which broaden the therapeutic spectrum for couples for whom IVF is indicated. NC-IVF could be considered in patients with poor prognosis for cIVF due to low ovarian reserve. Age is the main prognostic factor and results are acceptable up to 40 years of age. The main limiting factor is the risk of cancellation due to ovulation, which can be reduced through different strategies. Pregnancy rate per embryo transfer results are encouraging.
Clinical pregnancy resulting from intracytoplasmic sperm injection of prematurely ovulated oocytes retrieved from the posterior cul-de-sac
2021, F and S Reports
To report a clinical pregnancy resulting from intracytoplasmic sperm injection of prematurely ovulated oocytes retrieved from the posterior cul-de-sac.
Case report.
Academic center.
A 40-year-old nulligravid woman underwent ovarian stimulation for in vitro fertilization (IVF). Daily injections of gonadotropin-releasing hormone antagonist were initiated on cycle day 8. A 10,000 IU dose of human chorionic gonadotropin was administered on cycle day 15 to trigger follicular maturation. The estradiol and luteinizing hormone levels on the trigger day were 1528 pg/mL and 2.4 mIU/mL, respectively. The patient underwent oocyte retrieval 35 hours after the trigger. Transvaginal sonography at the time of the retrieval revealed a large pocket of free fluid in the posterior cul-de-sac. Only 3 follicles measuring 10–12 mm were noted in both ovaries. No lead follicles were visualized.
Aspiration of free fluid from the posterior cul-de-sac.
Clinical pregnancy.
The fluid in the posterior cul-de-sac was aspirated, and 3 mature oocytes were retrieved. Aspiration of the smaller ovarian follicles measuring 10–12 mm did not yield oocytes. All mature oocytes retrieved from the posterior cul-de-sac were fertilized with intracytoplasmic sperm injection. Three cleavage-stage embryos were transferred 3 days later. A single intrauterine pregnancy with cardiac activity was confirmed at a gestational age of 7 weeks.
In the setting of premature ovulation, aspiration of free fluid from the posterior cul-de-sac can result in the retrieval of mature oocytes, which may result in clinical pregnancies.
The impact of indomethacin on the number of oocytes retrieved and IVF outcomes in patients with poor ovarian response
2021, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Despite the absence of significant relationship, the authors noted that indomethacin had a significant effect in reducing PO among patients who did not have an LH surge on hCG day (OR: 8.29, 95% CI: 1.63–42.3, p = 0.009). In our study, we found that indomethacin had a significant impact on preventing cycle cancellation due to PO among infertile patients with POR (β = -1.931, standard error = 0.832, Exp(B) = 0.145, p = 0.020), as similar to the findings reported by Kawachiya et al. [13] and Kadoch et al. [14]. Based on these data, it is feasible to conclude that indomethacin administration can reduce PO-related cycle cancellation by 85% (1–0.145) among PORs.
The aim of this retrospective case-control study was to analyze the effect of administering indomethacin after triggering final oocyte maturation in patients with poor ovarian response (POR) on the cycle cancellation rate due to premature ovulation (PO), the number of oocytes retrieved and the clinical outcomes of IVF cycles.
A total of 214 patients with POR, diagnosed according to the Bologna criteria, who underwent fresh IVF cycle via flexible gonadotrophin-releasing hormone antagonist (GnRH-ant) protocol were enrolled in the study. The control group consisted of 100 patients, whereas the indomethacin group included 114 patients who received 100 mg rectal indomethacin administered twice within the same day (twelve hours apart) –starting at twelve hours after triggering. Cycle cancelation rates (CCR), number of oocytes retrieved (nOR), implantation rates (IR), biochemical pregnancy (BP) and clinical pregnancy loss rates (CPL), ongoing pregnancy rates (OPR) and live birth rates (LBR) were compared between the indomethacin and control groups.
The CCR rate was significantly lower in the indomethacin group (1.8%) compared to the control group (1.8% vs %12%, p = 0.01). In the control group, those with cycle cancellation were older than those without cycle cancellation (mean age 42.2 ± 2.3 years vs. 39.36 ± 4.3 years, p = 0.001) and had lower anti-Müllerian hormone levels and lower antral follicle count (0.59 ± 0.2 ng/mL vs 0.79 ± 0.2 ng/mL, p = 0.001 and 4 ± 0.6 vs 5.7 ± 1.7, p = 0.001, respectively). In multivariable analysis, when the dependent variable in the logistic regression model was coded as the absence of cycle cancellation, it was observed that only indomethacin had a statistically significant effect on cycle cancellation (β = −1.931, standard error = 0.832, Exp(B) = 0.145, p = 0.020). nOR was higher in the indomethacin group than control group but the difference did not reach significance (p = 0.07). Moreover, the IR, OPR and LBR, BP and CPL values were similar in the indomethacin and control groups (p > 0.05).
Based on data from this study, it can be concluded that indomethacin reduces cycle cancelation due to PO in patients with POR –without compromising implantation and pregnancy rates. However, further randomized controlled trials with larger sample sizes are required to clarify the definitive effect of indomethacin in the treatment of patients with POR.
Analgesic use at ovulation and implantation and human fertility
2020, American Journal of Obstetrics and Gynecology
Studies investigating the effects of pain-relieving medication use on conceiving a pregnancy have shown conflicting results. Furthermore, no previous study has examined medication use around ovulation or implantation and the associations with the probability of conception, fecundability.
The objective of the study was to explore the association between fecundability and analgesic use in 3 different menstrual cycle windows (preovulation, periovulation, and implantation) as well as across the entire menstrual cycle.
We analyzed data from a prospective cohort study of women between 30 and 44 years of age who were trying to conceive naturally from 2008 through 2015. Using daily diaries, medication usage was classified as acetaminophen, aspirin, or nonaspirin nonsteroidal antiinflammatory drug during 4 time periods of interest (preovulatory, periovulatory, and implantation) as well as the overall nonmenstrual bleeding days of the cycle. Menstrual cycles during the prospective attempt to become pregnant were enumerated using daily diary menstrual bleeding information. Conception was defined as a positive home pregnancy test. Discrete time fecundability models were used to estimate the fecundability ratio and 95% confidence interval in each of the 4 time windows of interest and for each pain reliever (aspirin use, nonaspirin nonsteroidal antiinflammatory drug use, acetaminophen) compared with no medication use after adjustment for several covariates including age, race, education, body mass index, alcohol and caffeine use, frequency of intercourse, and a history of migraines or uterine fibroids.
Medication use was infrequent in the 858 women and 2366 cycles in this analysis. Use of nonaspirin nonsteroidal antiinflammatory drugs or acetaminophen was not associated with fecundability in any of the time windows of interest. Although the sample size was small, aspirin use during the implantation window was associated with increased fecundability (adjusted fecundability ratio [confidence interval]: 2.05 [1.23–3.41]). This association remained when limiting the analysis to cycles with minimal missing data or when adjusting for gravidity. None of the other medications were associated with fecundability.
Aspirin use around implantation was associated with increased fecundability. These results expand previous literature to suggest the following: (1) implantation may be an important target for the effects of aspirin on conception and (2) aspirin may be beneficial, regardless of pregnancy loss history. These observations should be tested with a clinical trial.
Successful prevention of follicular rupture at 45 h after hCG and GnRHa triggering by emergent administration of indomethacin: A case report
2018, Taiwanese Journal of Obstetrics and Gynecology
To report the management and prevention of pre-operative ovulation before oocyte retrieval with emergent administration of indomethacin.
During in vitro fertilization (IVF) treatment, the patient described here mistakenly administered 6500 IU of hCG and 0.2 mg of triptorelin (GnRHa) 9 h earlier than scheduled triggering. To avoid emergent oocyte retrieval in the midnight, indomethacin was given (150 mg/day, there times a day) from 2 h after incorrect hCG and GnRHa injection to the night before ovum pickup. The oocyte retrieval was performed at originally scheduled time. The result showed that pre-operative ovulation was effectively prevented and we successfully collected the expected number Andersen et al., 1995 of oocytes at 45 h after triggering.
The presented case demonstrates that indomethacin can be used safely and effectively as an emergent prescription to prevent and postpone ovulation till up to 45 h after hCG and GnRHa triggering.
Age, independent from ovarian reserve status, is the main prognostic factor in natural cycle in vitro fertilization
2016, Fertility and Sterility
To analyze natural cycle IVF (NC-IVF) results according to patient age, ovarian reserve status following the Bologna criteria, cause of infertility, and modification of the cycle with the use of GnRH antagonist.
Retrospective cohort study.
Tertiary-care university hospital.
Nine hundred forty-seven natural cycles carried out in 320 patients.
Analysis of 947 NC-IVF outcomes performed in one single center between January 2010 and December 2014.
Pregnancy rates per cycle started, per ET, and per patient, as well as ongoing pregnancy rate at a minimum of 12 weeks of gestation.
Among the three age groups analyzed (≤35 years, 36–39 years, and ≥40 years), pregnancy rates per cycle were significantly lower in the older group of patients (11.4% vs. 11.6% vs. 5.9%). In addition, miscarriage rate (7.7% vs. 34.4% vs. 50%) and ongoing pregnancy rate (10.6% vs. 7.6%vs. 3.0%) were negatively affected by patient age. However, no differences were observed according to patient ovarian reserve status, cause of infertility, or modification of the cycle with GnRH antagonist. The multivariate logistic regression confirmed that patient age was the only variable that could predict pregnancy in NC-IVF cycles (odds ratio, 0.93; 95% confidence interval, 0.88–0.98).
NC-IVF is a feasible and “patient-friendly” option to be offered to young patients, independent of their ovarian reserve status.

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ArticleSpontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin

Abstract

Section snippets

Fertility and Sterility

Fertility and Sterility

Reproductive BioMedicine Online

Indomethacin effect on implantation rates in oocyte recipients

Human Reproduction

Follicular arrest during the midfollicular phase of the menstrual cycle; a gonadotropin-releasing hormone antagonist imposed follicular–follicular transition

Journal of Clinical Endocrinology and Metabolism

Article
Spontaneous ovulation rate before oocyte retrieval in modified natural cycle IVF with and without indomethacin