Intrauterine insemination with donor sperm: only the number of motile spermatozoa inseminated influences both pregnancy and live-birth rates

Abstract Study question Are live birth rates after IUI with donor sperm (IUI-D) and controlled ovarian stimulation comparable between women with a spontaneous LH peak vs those without? Summary answer Biochemical, clinical, ongoing pregnancy rates and live birth rates were higher among women without an LH peak. What is known already It is common clinical practice to trigger ovulation in IUI cycles once specific criteria are met; if a natural LH surge appears, adjusting the IUI timing may become necessary. Pregnancy rates seem to be slightly better when IUI is scheduled in relation to the presence or absence of an LH peak in non-stimulated cycles. In IUI with stimulated cycles, however, there is no consensus in the medical literature regarding the best moment to program the IUI, due to different inclusion criteria, different IUI timing and definition of LH peak among studies. Study design, size, duration Retrospective cohort study of 9,657 IUI-D cycles performed between 2012 and 2019 in one fertility center. IUI-D without LH peak (n = 6,679) versus IUI-D with LH peak (n = 2,978) were compared. Differences in pregnancy outcomes between study groups were evaluated using a Pearson’s Chi2 test. A p < 0.05 was considered statistically significant. Participants/materials, setting, methods The definition used to define an LH peak is > 10UI/L in the last follicular control. In cases without an LH peak, when at least one dominant follicle reached 17mm, ovulation was triggered with human chorionic gonadotropin in the following 24h, and IUI-D was performed 38h after triggering. In cases with an LH peak, ovulation was triggered the 6h following the detection, and IUI-D was also performed 38h later. Main results and the role of chance The women BMI and age were comparable between groups, with a mean±SD of 35.2±4.8 years old, and 24.3±4.7 for BMI. Other characteristics such as number of previous inseminations, type of stimulation drug, initial dose, total dose, stimulation length and number of follicles > 16mm in the last follicular control were also comparable. As expected, the LH level at the last follicular control was different between groups, with a mean of 5.1UI/L in the no-LH peak and 21.4IU/L in the LH peak group. The group without an LH peak had higher biochemical, clinical, ongoing and live birth rates compared to the group with LH peak: 27.7% vs. 20.7%; 19.5% vs. 15.5%; 17.7% vs. 13.7%; 16.3% vs. 12.6%, respectively (p-value<0.001). Limitations, reasons for caution The main limitation of the study is its retrospective nature. Also, a definition of LH peak based in absolute values was used; a definition based in relative values may lead to different results. Wider implications of the findings: A definition of LH peak based on absolute numbers is imprecise, and the cut-off of 10UI/L does not allow a good scheduling for IUI. A LH peak based on relative values could improve the detection of patients starting ovulation and the accuracy in programming IUI. Trial registration number Not applicable

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The addition of GnRH antagonists in intrauterine insemination cycles with mild ovarian hyperstimulation does not increase live birth rates--a randomized, double-blinded, placebo-controlled trial

Human Reproduction ◽

10.1093/humrep/der033 ◽

2011 ◽

Vol 26 (5) ◽

pp. 1104-1111 ◽

Cited By ~ 23

Author(s):

A. E. P. Cantineau ◽

B. J. Cohlen ◽

H. Klip ◽

M. J. Heineman ◽

A. Hoek ◽

...

Keyword(s):

Live Birth ◽

Intrauterine Insemination ◽

Controlled Trial ◽

Ovarian Hyperstimulation ◽

Birth Rates ◽

Gnrh Antagonists ◽

Live Birth Rates ◽

Double Blinded

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Erratum to ‘Cumulative live birth rates following insemination with donor sperm in single women, same-sex couples and heterosexual patients: a 13-year, single-centre cohort study of 8.922 consecutive cycles’ [Reproductive BioMedicine Online 41 (year) 1007-1014]

Reproductive BioMedicine Online ◽

10.1016/j.rbmo.2021.05.012 ◽

2021 ◽

Author(s):

Elena Linara ◽

Daniel Bodri ◽

Jinjun Wang ◽

Mimi Arian-Schad ◽

Nick Macklon ◽

...

Keyword(s):

Cohort Study ◽

Live Birth ◽

Single Women ◽

Same Sex ◽

Single Centre ◽

Birth Rates ◽

Donor Sperm ◽

Same Sex Couples ◽

Live Birth Rates ◽

Cumulative Live Birth

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Ovulation Induction with Oral Agents for Women 38 Years and Older Yields Low Live Birth Rates with Intrauterine Insemination Regardless of Ovarian Reserve

Fertility and Sterility ◽

10.1016/j.fertnstert.2014.12.012 ◽

2015 ◽

Vol 103 (2) ◽

pp. e11

Author(s):

E. Barnard ◽

Z. Khan ◽

D. Morbeck ◽

J. Jensen

Keyword(s):

Live Birth ◽

Ovarian Reserve ◽

Ovulation Induction ◽

Intrauterine Insemination ◽

Birth Rates ◽

Live Birth Rates ◽

Oral Agents

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Gonadotrophins or clomiphene citrate in women with normogonadotropic anovulation and CC failure: does the endometrium matter?

Human Reproduction ◽

10.1093/humrep/deaa052 ◽

2020 ◽

Vol 35 (6) ◽

pp. 1319-1324

Author(s):

E M Bordewijk ◽

N S Weiss ◽

M J Nahuis ◽

J Kwee ◽

A F Lambeek ◽

...

Keyword(s):

Live Birth ◽

Treatment Effect ◽

Endometrial Thickness ◽

Intrauterine Insemination ◽

Controlled Trial ◽

Clomiphene Citrate ◽

Live Birth Rate ◽

Ovulatory Cycle ◽

Birth Rates ◽

Live Birth Rates

Abstract STUDY QUESTION Is endometrial thickness (EMT) a biomarker to select between women who should switch to gonadotropins and those who could continue clomiphene citrate (CC) after six failed ovulatory cycles? SUMMARY ANSWER Using a cut-off of 7 mm for EMT, we can distinguish between women who are better off switching to gonadotropins and those who could continue CC after six earlier failed ovulatory CC cycles. WHAT IS ALREADY KNOWN For women with normogonadotropic anovulation, CC has been a long-standing first-line treatment in conjunction with intercourse or intrauterine insemination (IUI). We recently showed that a switch to gonadotropins increases the chance of live birth by 11% in these women over continued treatment with CC after six failed ovulatory cycles, at a cost of €15 258 per additional live birth. It is unclear whether EMT can be used to identify women who can continue on CC with similar live birth rates without the extra costs of gonadotropins. STUDY DESIGN, SIZE, DURATION Between 8 December 2008 and 16 December 2015, 666 women with CC failure were randomly assigned to receive an additional six cycles with a change to gonadotropins (n = 331) or an additional six cycles continuing with CC (n = 335), both in conjunction with intercourse or IUI. The primary outcome was conception leading to live birth within 8 months after randomisation. EMT was measured mid-cycle before randomisation during their sixth ovulatory CC cycle. The EMT was available in 380 women, of whom 190 were allocated to gonadotropins and 190 were allocated to CC. PARTICIPANTS/MATERIALS, SETTING, METHODS EMT was determined in the sixth CC cycle prior to randomisation. We tested for interaction of EMT with the treatment effect using logistic regression. We performed a spline analysis to evaluate the association of EMT with chance to pregnancy leading to a live birth in the next cycles and to determine the best cut-off point. On the basis of the resulting cut-off point, we calculated the relative risk and 95% CI of live birth for gonadotropins versus CC at EMT values below and above this cut-off point. Finally, we calculated incremental cost-effectiveness ratios (ICER). MAIN RESULTS AND THE ROLE OF CHANCE Mid-cycle EMT in the sixth cycle interacted with treatment effect (P < 0.01). Spline analyses showed a cut-off point of 7 mm. There were 162 women (45%) who had an EMT ≤ 7 mm in the sixth ovulatory cycle and 218 women (55%) who had an EMT > 7 mm. Among the women with EMT ≤ 7 mm, gonadotropins resulted in a live birth in 44 of 79 women (56%), while CC resulted in a live birth in 28 of 83 women (34%) (RR 1.57, 95% CI 1.13–2.19). Per additional live birth with gonadotropins, the ICER was €9709 (95% CI: €5117 to €25 302). Among the women with EMT > 7 mm, gonadotropins resulted in a live birth in 53 of 111 women (48%) while CC resulted in a live birth in 52 of 107 women (49%) (RR 0.98, 95% CI 0.75–1.29). LIMITATIONS, REASONS FOR CAUTION This was a post hoc analysis of a randomised controlled trial (RCT) and therefore mid-cycle EMT measurements before randomisation during their sixth ovulatory CC cycle were not available for all included women. WIDER IMPLICATIONS OF THE FINDINGS In women with six failed ovulatory cycles on CC and an EMT ≤ 7 mm in the sixth cycle, we advise switching to gonadotropins, since it improves live birth rate over continuing treatment with CC at an extra cost of €9709 to achieve one additional live birth. If the EMT > 7 mm, we advise to continue treatment with CC, since live birth rates are similar to those with gonadotropins, without the extra costs. STUDY FUNDING/COMPETING INTEREST(S) The original MOVIN trial received funding from the Dutch Organization for Health Research and Development (ZonMw number: 80-82310-97-12067). C.B.L.A. reports unrestricted grant support from Merck and Ferring. B.W.M. is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for Merck, ObsEva, IGENOMIX and Guerbet. All other authors have nothing to declare. TRIAL REGISTRATION NUMBER Netherlands Trial Register, number NTR1449

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