Can anti-Müllerian hormone predict success outcomes in donor sperm inseminations?

Anti-Müllerian hormone (AMH) is a useful biomarker to predict the ovarian response to controlled ovarian stimulation (COS) for IVF. However, currently there is a lack of evidence for the role of ovarian reserve markers when there is no need of COS. The aim of this study was to evaluate the usefulness of AMH to predict the outcomes of donor sperm insemination cycles in non-infertile women. A retrospective study including 139 healthy women, who underwent 348 intrauterine insemination (IUI) cycles with donor sperms under the stimulated or natural cycles, was conducted. All patients had an AMH evaluation performed before starting the first IUI attempt. AMH levels were similar in both, women who conceived and those who did not (2.00 ± 1.52 vs. 1.88 ± 1.64 ng/ml; p = .45). The area under the ROC curve in predicting pregnancy for AMH was 0.53. After adjusting for other confounding variables, the multivariate analysis revealed that AMH was not associated with pregnancy (aOR 0.89; 95% CI 0.57-1.37). We conclude that AMH is not predictive of pregnancy in healthy non-infertile women who perform IUI with donor sperm. These findings suggest the low capability of AMH to predict fertility when no COS is needed.

Clinical success of IUI cycles with donor sperm is not affected by total inseminated volume: a RCT.

STUDY QUESTION: What is the impact on live birth rates (LBR) when a donor IUI (dIUI) cycle is performed with an insemination volume of 0.5 mL versus the usual 0.2 mL? SUMMARY ANSWER: LBR after a dIUI cycle is no different when performed with 0.5 versus 0.2 mL. WHAT IS ALREADY KNOWN: An IUI has an important role in the treatment of severe male infertility, and is often used in same-sex female couples and single parents. Different variables have been studied to determine factors correlated with clinical outcomes (IUI scheduling, ovarian stimulation, sperm parameters) but little is known about the inseminated volume. The use of conical bottom test tubes could contribute substantially to the loss of inseminated spermatozoa because it precludes the total recovery of the sample. Additionally, the insemination catheter could uphold this reduction causing sperm adhesion on the inner walls of the insemination catheter, decreasing even more the total inseminated volume. It is expected that utilizing an IUI approach that increases sperm volume in the fallopian tubes (0.5 mL rather than 0.2 mL) at the time of ovulation will lead to higher LBRs. To avoid bias related to sperm quality, the study population was restricted to dIUI cycles. STUDY DESIGN SIZE AND DURATION: A parallel-group, double-blinded, RCT, including patients undergoing natural or stimulated dIUI, was performed between March 2013 and April 2015. dIUI cycles (n = 293) were randomized through a computer-generated list to undergo insemination with 0.2 mL (control group) or 0.5 mL (study group), of which 24 were excluded (protocol deviation) and 269 received the allocated intervention. Patients with the presence of tubal factor infertility, grades III-IV endometriosis, >3 previous dIUI cycles or with ≥3 follicles >14 mm were excluded. The study was designed with 80% power to detect a 5% difference in LBR with a reference of 15% and a two-tailed 5% significance level. The required sample size was 118 per group. PARTICIPANTS/MATERIALS SETTING AND METHOD: There were 143 cycles (0.2 mL group) and 126 cycles (0.5 mL group). The primary end-point of the trial was LBR per dIUI cycle in both treatment groups. Clinical pregnancy rate and miscarriage rate were evaluated as secondary outcomes. MAIN RESULTS AND THE ROLE OF CHANCE: No adverse events were reported during the study trial. Study groups (0.2 versus 0.5 mL, respectively) were similar in age (35.8 ± 3.9 versus 35.4 ± 4.0 years: mean±SD), and had similar anti-Mullerian hormone levels (2.2 ± 1.8 versus 2.0 ± 1.5 ng/mL), basal antral follicle count (13.2 ± 6.4 versus 13.6 ± 6.0), BMI (23.5 ± 3.9 versus 23.7 ± 4.1 kg/m2), number of follicles >17 mm (1.1 ± 0.5 versus 1.1 ± 0.5), total gonadotrophin dose (553.1 ± 366.3 versus 494.6 ± 237.1 IU), and total motile sperm count (8.22 ± 7.1 versus 7.7 ± 5.7 million). Similar clinical pregnancy rates (18.9% (27/143) versus 19.8% (25/126), NS), LBRs (15.4% (22/143) versus 19.0% (24/126), NS) and miscarriage rates (18.5% (5/27) versus 4.0% (1/25), NS) were observed between groups. LIMITATIONS REASONS FOR CAUTION: The study was not powered to detect differences in the secondary outcomes, clinical pregnancy and miscarriage rates. The randomization was performed at the dIUI cycle level, therefore, the results are reported as success rate per dIUI cycle rather than per patient. WIDER IMPLICATIONS OF THE FINDINGS: This is the first RCT to show that the inseminated volume is not correlated with the probability of a live birth. The miscarriage rate was higher in the 0.2 mL group, although this difference was not statistically significant. If the lower miscarriage rate observed in the 0.5 mL group is confirmed, this could be related to the presence of uterine contractions similar of those generated during sexual intercourse, which may be implicated in the inception of early biochemical embryo-endometrium communication. STUDY FUNDING/COMPETING INTERESTS: All authors declare having no conflict of interest with regard to this trial. No funding was received for this study. This research was performed under the auspices of 'Càtedra d'Investigació en Obstetrícia I Ginecologia' of the Department of Obstetrics, Gynaecology and Reproductive Medicine, Hospital Universitari Quiron-Dexeus, Universitat Autònoma de Barcelona. TRIAL REGISTRATION NUMBER: The trial was registered at clinicaltrials.gov (Identifier: NCT03006523).

Should progesterone on the human chorionic gonadotropin day still be measured?

OBJECTIVE: To evaluate in our setting whether there is currently a level of P on the hCG day (P-hCG) predictive of no pregnancy. DESIGN: Observational study of prospectively collected data of the P-hCG levels of stimulated IVF cycles. SETTING: In vitro fertilization unit. PATIENT(S): All cycles of IVF/intracytoplasmic sperm injection with fresh embryo transfer performed between January 2009 and March 2014. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy rate. RESULT(S): Clinical pregnancy rate per ET was 38.7% and live birth rate was 29.1%. The P-hCG concentration was positively correlated to E2 on the hCG day, and the number of oocytes was negatively correlated to age. Progesterone on hCG day was higher among agonist- compared with antagonist-treated patients (mean ± SD: 1.13 ± 0.69 ng/mL vs. 0.97 ± 0.50 ng/mL) and among recombinant FSH compared with recombinant FSH + hMG stimulation (mean ± SD: 1.11 ± 0.58 ng/mL vs. 0.94 ± 0.50 ng/mL). Pregnancy rate was positively associated with the number of oocytes. There was no correlation between P-hCG value and pregnancy rate, overall or according to the type of treatment. CONCLUSION(S): In our setting there is no P-hCG value differentiating a good from a poor cycle success rate. CLINICAL TRIAL REGISTRATION NUMBER: NCT02323347.

Antagonist rescue of agonist IVF cycle at risk of OHSS: a case series.

We describe a series of in vitro fertilisation (IVF) long protocol cycles presenting a risk of ovarian hyperstimulation syndrome (OHSS) which were rescued with an antagonist at a university-based tertiary-care fertility centre. Nineteen IVF patients presenting a risk of OHSS during treatment with long protocol, between 2009 and November 2012 were included in the present study. After discussion of available options, the agonist was stopped and a daily gonadotropin-releasing hormone (GnRH) antagonist injection was initiated ("rescue protocol") and maintained until ovulation trigger. Fourteen patients were triggered with human chorionic gonadotropin (hCG) and five with GnRH agonist bolus, yielding competent oocytes. Seventeen embryo transfers were performed in the fresh cycles. One patient developed moderate OHSS. There were eight clinical pregnancies after the fresh IVF cycle (42% per patient), and six further pregnancies after frozen-thawed cycles, resulting in a 73% cumulative clinical pregnancy rate within one year. We conclude that the "rescue protocol with antagonist" of the long IVF cycle with a high risk of OHSS allows us to carry on with the cycle, without compromising its success or the patient safety, thus broadening the possibility of applying the long protocol.

GnRH antagonist rescue of a long-protocol IVF cycle and GnRH agonist trigger to avoid ovarian hyperstimulation syndrome: three case reports.

OBJECTIVE: To describe three clinical cases involving patients at high risk of severe ovarian hyperstimulation syndrome (OHSS) during IVF stimulation. DESIGN: Description of clinical management of IVF cycles and outcomes in patients at risk of developing OHSS. SETTING: Reproductive medicine unit, private hospital. PATIENT(S): Three infertile patients undergoing stimulation for IVF/intracytoplasmic sperm injection presenting high risk of OHSS. INTERVENTION(S): IVF patients treated under long protocol presenting high risk of OHSS had their cycles rescued by withdrawing the agonist and replacing it with an antagonist and triggering ovulation with an agonist bolus. MAIN OUTCOME MEASURE(S): OHSS symptoms, pregnancy. RESULT(S): None of the three patients developed OHSS. One patient got pregnant after fresh embryo transfer, one patient got pregnant after frozen embryo transfer, and one patient had no oocytes retrieved despite the detection of LH in urine after the GnRH bolus. CONCLUSION(S): When a patient undergoing an IVF cycle with long protocol is at high risk of severe OHSS, rescuing the cycle by withdrawing the agonist and replacing it with an antagonist and triggering ovulation with an agonist bolus could be considered without jeopardizing the safety of the patient while retaining the opportunity for success of the cycle. Further broader studies are needed.

Effect of using an echogenic catheter for ultrasound-guided embryo transfer in an IVF programme: a prospective, randomized, controlled study.

BACKGROUND: Recent evidence showed that ultrasound-guided embryo transfer significantly increases successful implantation compared to the clinical touch method. It has been postulated that new echodense catheters which are more readily detectable by ultrasound may refine transfer techniques even more, thus improving IVF outcome. METHODS: A prospective, randomized, controlled trial comparing IVF outcome for women undergoing embryo transfer under ultrasound guidance by a single healthcare provider with random assignment according to a computer-generated randomization table to either standard soft Wallace catheter (standard catheter group, n=95) or the new echogenic soft Wallace catheter (echogenic catheter group, n=98). RESULTS: The use of the echodense catheter facilitated catheter identification under ultrasound, and thus the duration of the embryo transfer procedure since the loaded catheter was handed to the physician and up to embryo discharge was significantly shorter in the echogenic catheter group as compared with the standard catheter group. There were 39 and 53 clinical pregnancies in the standard catheter (41%) and echogenic catheter (54.1%) groups, respectively. This was not statistically significant (P=0.08) according to the OR (0.6) and CIs (0.33-1.04). However, twin pregnancy rate was significantly increased (P<0.01) with the use of the new catheter which was the underlying source for obtaining significant increase in implantation rate in this group (37.1%) as compared with the standard catheter group (23.2%). CONCLUSION: This pilot study suggests that the use of the echogenic Wallace catheter simplifies ultrasound-guided embryo transfer but not definite benefit in terms of pregnancy rates was obtained. In contrast, the use of the new catheter was associated with a significant increase in the number of twin pregnancies.

Use of a prediction model for high-order multiple implantation after ovarian stimulation with gonadotropins.

OBJECTIVE: To determine prospectively the effectiveness in clinical practice of a prediction model for high-order multiple pregnancies (HOMP) (triplets or more). DESIGN: Prospective study. SETTING: University teaching hospital. PATIENT(S): Eight hundred forty-nine consecutive infertile patients undergoing a total of 1,542 treatment cycles. INTERVENTION(S): Gonadotropin ovarian stimulation or induction of ovulation without IVF MAIN OUTCOME MEASURE(S): Observed and predicted overall pregnancy rates and the incidence of HOMP. RESULT(S): The use of the prediction model (implying cancellation of all cycles at high risk for HOMP) would result in an 8% (95% confidence interval, 6.8%-9.2%) reduction of overall pregnancy rate but also in a 285% (95% CI, 279%-291%) reduction of HOMP. CONCLUSION(S): By using our prediction model, it was possible to maintain a low risk of HOMP with a good pregnancy rate in patients receiving gonadotropin ovarian stimulation or induction of ovulation without IVF.

Serum progesterone concentrations on the day of HCG administration cannot predict pregnancy in assisted reproduction cycles.

The effect of subtle rises of progesterone in the late follicular phase of cycles of ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonists on pregnancy outcome is controversial. This study used receiver-operating characteristic (ROC) analysis to gain further insight into the predictive value of serum progesterone concentrations on the day of human chorionic gonadotrophin (HCG) injection in normally responding patients receiving the long protocol of GnRH agonist (group L; n = 218) and in low responders receiving the short ('flare-up') protocol (group S; n = 159). ROC analysis showed that serum progesterone concentration on the HCG day was not indicative of conception and non-conception cycles in the whole population studied, in group L or in group S. To further assess the potential impact of 'high' concentrations of circulating progesterone on the day of HCG administration on pregnancy rates and outcome, the threshold value (<0.9 ng/ml) to discriminate between women with 'high' (group H; n = 197) and 'normal' (group N; n = 180) progesterone was applied. No significant differences were found with respect to pregnancy and miscarriage rates between these two groups. Serum progesterone concentrations on the day of HCG administration therefore cannot predict pregnancy in assisted reproduction cycles using GnRH agonists and gonadotrophins.