The impact of the Dobbs decision on in-vitro fertilization and fertility care.

PURPOSE OF REVIEW: The 2022 Supreme Court ruling in Dobbs vs Jackson marks a frightening new reality in America. Physicians and patients have been left confused and concerned regarding the broader implications of this ruling. Now that the constitutional right to an abortion has been overturned and the power has been relinquished to individual states, there is justifiable concern regarding the impact on in-vitro fertilization (IVF). This review explores the ways IVF and fertility care are at risk in the context of our new reality. RECENT FINDINGS: The decision to overturn the right to an abortion without specifying a viability standard opens the door to interpretation of when 'life' begins. Laws that do not specifically exempt IVF, or that include language suggesting that 'life begins at fertilization' pose a real threat to IVF. The potential for personhood laws poses a threat to embryo freezing and disposition, preimplantation genetic testing and culpability among other concerns. SUMMARY: Limitations to IVF may become an unintended consequence to the Dobbs decision, making IVF less efficient, more costly and unsafe, and inevitably limiting access to care. It is therefore crucial that public health legislation be rooted in science and not dictated by religion or politics. Physicians must act alongside legislators to protect reproductive freedom and access to care.

Evaluation of the cost-effectiveness of ovulation suppression with progestins compared with GnRH analogs in assisted reproduction cycles.

RESEARCH QUESTION: Is ovulation suppression with progestins, requiring a freeze-all approach and subsequent frozen embryo transfer resulting from progestenic endometrial changes, cost-effective compared with gonadotropin releasing hormone analogues (GnRH) during assisted reproduction cycles. DESIGN: Cost-effectiveness analysis derived from a PubMed literature search of average US costs of GnRH agonist and antagonist IVF cycles. RESULTS: In all fresh IVF cycle models, progestin cycles were more expensive owing to the additional costs of increased gonadotropin use, embryo freezing and subsequent frozen embryo transfer (FET). The average cost per live birth with progestins ($32,466-$56,194) was higher than fresh IVF cycles with short (flare) GnRH agonist ($4,447-$12,797 higher) and GnRH antagonist ($1,542-$9,893 higher). When analyzing an initial embryo transfer plus additional FET in patients not initially pregnant, progestin cycles were still more expensive per live birth compared with conventional protocols. When planned freeze only cycles were analyzed, progestins became more cost-effective per live birth compared with antagonist cycles ($2,079 lower) but remained more expensive than short agonist cycles ($823 more expensive). CONCLUSIONS: Ovulation inhibition in IVF using progestins requires a freeze-only approach of embryos, and thus progestin use was not cost-effective compared with fresh embryo transfer cycles. Progestins, however, may be cost-effective compared with GnRH antagonist in planned freeze only cycles such as in preimplantation genetic testing or fertility preservation.

Compliance on Mandatory Data Reporting in Registered Obstetrics Trials.

BACKGROUND: The Food and Drug Administration's (FDA's) Amendments Act established a legal mandate requiring registration of certain drug, device, and biologics trials in ClinicalTrials.gov prior to patient enrollment. One provision of the act requires investigators to report trial results in ClinicalTrials.gov within 1 year of completion. Preliminary evidence suggests that overall compliance rates are inadequate, and rates specific to obstetrics have not been investigated. OBJECTIVE: The purpose of this study was to examine the rate of compliance for mandatory reporting of results from obstetrics trials to ClinicalTrials.gov and to determine whether compliance rates were associated with funding type. STUDY DESIGN: We performed a registry-based study of clinical trials pertaining to obstetrics. ClinicalTrials.gov was cross-referenced with Drugs@FDA to determine which trials required mandatory reporting. We used obstetrics trials registered on ClinicalTrials.gov with at least 1 US site. Phase 0, Phase 1, and trials not reporting a phase were excluded. Furthermore, only trials of interventions approved by the FDA were retained. RESULTS: Our search returned 973 trials, of which 325 (33.4%) were screened for eligibility. Of the 325 completed trials, 74 (22.8% or 7.6% of the total) met all inclusion criteria and were evaluated for compliance. Thirty-seven of these trials (50%) did not list results, whereas the remaining 37 trials (50%) contained results on ClinicalTrials.gov. Trials funded by the National Institutes of Health (87.5%; ⅞) and industry (80%; 12/15) had higher rates of compliance than trials funded by other (43.9%; 18/41) or unspecified (0%; 0/10) sources. CONCLUSION: Half of all applicable obstetrics trials did not report results. Furthermore, rates of compliance appeared to vary by funding source, with trials funded by the National Institutes of Health or industry appearing to have a higher rate of compliance to mandatory data reporting. Greater awareness of federal regulations is needed, and changes should be implemented to increase reporting.

Fertility and Endometriosis.

Approximately 30% to 50% of women that have the diagnosis of endometriosis also struggle with infertility. Twenty five percent to 50% of women diagnosed with infertility also have endometriosis, but the endometriosis may not be severe enough to be the primary etiology of infertility. White women have been reported to be more likely than African American women to have endometriosis. In addition, risk factors for endometriosis include below average body mass index, smoking, and alcohol use. Below is a discussion regarding the various ways in which endometriosis decreases fecundity and also discusses potential outcomes of fertility treatments regarding endometriosis.

Clinical Question: Does Medical Evidence Support Routine Oronasopharyngeal Suction at Delivery?

Oronasopharyngeal suction (ONPS) is regularly performed in neonates at delivery in many hospitals across the country today. Although ONPS is a technique that has essentially become habitual for most obstetricians, its theorized usefulness to help promote expeditious lung aeration after delivery by removal of amniotic fluid, meconium, mucus and blood that may otherwise be aspirated by the newborn, is currently not recommended. ONPS can cause vagal stimulation-induced bradycardia and thus hypercapnea, iatrogenic infection due to mucous membrane injury, and development of subsequent neonatal brain injury due to changes in cerebral blood flow regulation, particularly in premature infants. Multiple studies that have been performed comparing routine use of ONPS to no intervention controls indicate that newborns receiving ONPS took a longer time to achieve normal oxygen saturations, caused apneic episodes, and caused disturbances in heart rate (mainly bradycardia) compared to the control groups. Although the ONPS groups revealed no significantly different APGAR scores at 1 and 5 minutes, the ONPS groups took longer than the control group to reach an arterial oxygen saturation greater than or equal to 92% in the first minutes of life. Currently, Neonatal Resuscitation Program guidelines discourage the use of or meconium-stained amniotic fluid and in the absence of obvious obstruction. Furthermore, this manuscript highlights various literature sources revealing that the routine use of ONPS at the time of delivery can cause more harm than good, if any good at all.

Assessment of clinical pregnancies in up to eight ovarian stimulation with intrauterine insemination treatment cycles in those unable to proceed with in vitro fertilization.

OBJECTIVE: To study the primary objective of clinical pregnancy (CP) rate per ovarian stimulation with intrauterine insemination (OS-IUI) treatment cycle in patients with repetitive cycles up to a maximum of 8 cycles. DESIGN: Retrospective cohort. SETTING: Large fertility clinic. PATIENTS: A total of 37,565 consecutive OS-IUI cycles from 18,509 patients were included in this study. INTERVENTIONS: Those with anovulatory diagnoses, tubal factor infertility, male factor infertility, using donor sperm, canceled cycles, and those with missing data for either baseline characteristics or outcome were excluded. The CP rate was analyzed using generalized estimating equations and controlled for age, stimulation protocol, and body mass index. MAIN OUTCOMES MEASURES: Clinical pregnancy was defined as intrauterine gestation with fetal heartbeat visible on ultrasound. RESULTS: A total of 37,565 consecutive OS-IUI cycles from 2002 through 2019 at a private practice facility were evaluated. All cycles met inclusion criteria and were used in generalized estimating equation modeling. Patients aged <35 years comprised 47.6% of the cohort. After adjustment for confounders, the mean predicted probability of CP for cycles one to 8 was 15.7% per cycle. The mean predicted probability of CP in aggregated data from cycles 2 to 4 was only 1.7% lower compared with cycle 1 as the referent (16.7% vs. 15.0%, 95% confidence interval [CI] 2nd: 0.88 {0.82, 0.95}, 3rd: 0.86 {0.79, 0.93}, 4th: 0.88 {0.79, 0.98}). However, the 15.0% mean predicted probability of CP for the second through the fourth cycle was concordant with the mean for all included cycles (15.7%). The mean predicted probability of CP of cycles 5 to 8 was not significantly different compared with the referent (16.7% vs. 16.1%, 95% CI 5th: 0.97 [0.85, 1.11], 6th: 0.93 [0.79, 1.10], 7th: 1.01 [0.81, 1.26], 8th: 1.01 [0.76, 1.34]). The modeling of consecutive cycles suggested that the adjusted cumulative predicted probability of CP from OS-IUI continues to increase with each of the 8 successive cycles. CONCLUSION: Clinical pregnancy rates are satisfactory in up to 8 consecutive OS-IUI treatment cycles. These data are useful for counseling, especially in those patients for whom in vitro fertilization is not financially or ethically feasible.

Low-dose aspirin in reproductive health: effects on menstrual cycle characteristics.

OBJECTIVE: To estimate the effect of daily 81 mg low-dose aspirin (LDA) on menstrual cycle length and hormone profiles. DESIGN: Secondary analysis of a trial evaluating the effect of daily LDA or placebo on live birth among women with one or two previous pregnancy losses. SETTING: University medical centers. PATIENT(S): A total of 915 regularly menstruating women who had at least one menstrual cycle (3,190 total cycles) in which pregnancy did not occur. INTERVENTION(S): Randomized allocation to LDA versus placebo. MAIN OUTCOME MEASURE(S): Menstrual cycle length and follicular and luteal phases were measured. Urinary pregnanediol glucuronide, follicle-stimulating hormone, luteinizing hormone, and estrone-3-glucuronide were assessed up to six times during the first two cycles. Generalized estimating equations estimated relative risk of short (<25th percentile: <27 days) and long (>75th percentile: ≥32 days) versus normal cycle length. Linear mixed models estimated mean hormone level differences with weights used to account for multiple cycles contributed per participant. RESULT(S): There were no significant differences in total menstrual cycle, follicular phase, or luteal phase length between LDA and placebo groups. LDA posed no greater risk of having a short versus normal-length or long versus normal-length follicular phase, or having a short versus normal-length or long versus normal-length luteal phase. There were no significant differences in hormone levels across the menstrual cycle between the LDA and placebo groups. CONCLUSION(S): Daily LDA use did not result in any changes to menstrual cycle, follicular phase, or luteal phase length or hormone levels across the menstrual cycle compared with placebo. CLINICAL TRIAL REGISTRATION NUMBER: NCT00467363.

Mature Follicle Count and Multiple Gestation Risk Based on Patient Age in Intrauterine Insemination Cycles With Ovarian Stimulation.

OBJECTIVE: To estimate the risk of a multiple gestation pregnancy in ovarian stimulation intrauterine insemination (IUI) cycles when stratified by patient age and mature follicle number. METHODS: We conducted a retrospective cohort study at a single private practice fertility center of IUI cycles performed from 2004 to 2017. Intervention(s) were ovarian stimulation and IUI if postwash total motile sperm count was more than 8 million. Mature follicles were defined as 14 mm or more as measured on the day of ovulation trigger. Main outcomes and measures were rates of clinical pregnancy and multiple gestation. RESULTS: We identified 24,649 women who underwent a total of 50,473 IUI cycles. Increasing the number of mature follicles from one to five at the time of IUI in women younger than age 38 years increased the clinical pregnancy rate from 14.6% to 21.9% (adjusted odds ratio [aOR] 1.6, 95% CI 1.4-1.9), almost entirely from a marked increase in multiple gestations per cycle from 0.6% to 6.5% (aOR 9.9, 95% CI 6.9-14.2). There was little increase in singleton pregnancies per IUI (14.1-16.4%) regardless of mature follicle number. The per-pregnancy twin and higher-order multiple gestation risk significantly increased (3.9-23.3%, P<.01 and 0.2-10.6%, P<.01, respectively) when comparing one with five mature follicles present at the time of IUI (P<.01). In women younger than age 38 years with more than three follicles present, more than one quarter of all pregnancies were multiples. Similar findings occurred in women aged 38-40 years. In women older than age 40 years, up to four follicles tripled the odds of pregnancy (aOR 3.1, 95% CI 2.1-4.5) while maintaining a less than 12% risk of multiple gestation per pregnancy and a 1.0% absolute risk of multiples. CONCLUSION: Caution should be used in proceeding with IUI after ovarian stimulation when there are more than two mature follicles in women younger than age 40 years owing to the substantially increased risk of multiple gestation without an improved chance of singleton clinical pregnancy.