Use of progesterone in assisted reproduction

Infertility treatment is associated with increased risk of postpartum hospitalization due to heart disease

Yamada R et al., 2024 · Journal of internal medicine · Free to read

Cardiovascular disease is a major cause of maternal mortality, but the extent to which infertility treatment is implicated in heart disease remains unclear. To evaluate the association between infertility treatment and postpartum heart disease. We designed a retrospective cohort study of patients who delivered in the United States between 2010 and 2018. The primary outcome was hospitalization within 12-month post-delivery due to heart disease (including ischemic heart disease, atherosclerotic heart disease, cardiomyopathy, hypertensive disease, heart failure, and cardiac dysrhythmias). We estimated the rate difference (RD) of hospitalizations among patients who conceived with infertility treatment and those who conceived spontaneously. Associations were expressed as hazard ratios (HRs) and 95% confidence intervals (CIs), derived from Cox proportional hazards regression after adjustment for potential confounders. Infertility treatment was recorded in 0.9% (n = 287,813) of 31,339,991 deliveries. Rates of heart disease hospitalizations with infertility treatment and with spontaneous conception were 550 and 355 per 100,000, respectively (RD 195, 95% CI: 143-247; adjusted HR 1.99, 95% CI: 1.80-2.20). The most important increase in risk was observed for hypertensive disease (adjusted HR 2.16, 95% CI: 1.92-2.42). This increased risk was apparent as early as 30-day post-delivery (HR 1.61, 95% CI: 1.39-1.86), with progressively increasing risk up to a year. Although the absolute risk of postpartum heart disease hospitalization is low, infertility treatment is associated with an increased risk, especially for hypertensive disease. These findings highlight the importance of timely postpartum follow-ups in patients who received infertility treatment.

Risk of Stroke Hospitalization After Infertility Treatment

Sachdev D et al., 2023 · JAMA network open · Free full text on PubMed Central

Stroke accounts for 7% of pregnancy-related deaths in the US. As the use of infertility treatment is increasing, many studies have sought to characterize the association of infertility treatment with the risk of stroke with mixed results. To evaluate the risk of hospitalization from hemorrhagic and ischemic strokes in patients who underwent infertility treatment. DESIGN, SETTING, This population-based, retrospective cohort study used data abstracted from the Nationwide Readmissions Database, which stores data from all-payer hospital inpatient stays from 28 states across the US, from 2010 and 2018. Eligible participants included individuals aged 15 to 54 who had a hospital delivery from January to November in a given calendar year, and any subsequent hospitalizations from January to December in the same calendar year of delivery during the study period. Statistical analysis was performed between November 2022 and April 2023. Hospital delivery after infertility treatment (ie, intrauterine insemination, assisted reproductive technology, fertility preservation procedures, or use of a gestational carrier) or after spontaneous conception. The primary outcome was hospitalization for nonfatal stroke (either ischemic or hemorrhagic stroke) within the first calendar year after delivery. Secondary outcomes included risk of stroke hospitalization at less than 30 days, less than 60 days, less than 90 days, and less than 180 days post partum. Cox proportional hazards regression models were used to estimate associations, which were expressed as hazard ratios (HRs), adjusted for confounders. Effect size estimates were corrected for biases due to exposure misclassification, selection, and unmeasured confounding through a probabilistic bias analysis. Of 31 339 991 patients, 287 813 (0.9%; median [IQR] age, 32.1 [28.5-35.8] years) underwent infertility treatment and 31 052 178 (99.1%; median [IQR] age, 27.7 [23.1-32.0] years) delivered after spontaneous conception. The rate of stroke hospitalization within 12 months of delivery was 37 hospitalizations per 100 000 people (105 patients) among those who received infertility treatment and 29 hospitalizations per 100 000 people (9027 patients) among those who delivered after spontaneous conception (rate difference, 8 hospitalizations per 100 000 people; 95% CI, -6 to 21 hospitalizations per 100 000 people; HR, 1.66; 95% CI, 1.17 to 2.35). The risk of hospitalization for hemorrhagic stroke (adjusted HR, 2.02; 95% CI, 1.13 to 3.61) was greater than that for ischemic stroke (adjusted HR, 1.55; 95% CI, 1.01 to 2.39). The risk of stroke hospitalization increased as the time between delivery and hospitalization for stroke increased, particularly for hemorrhagic strokes. In general, these associations became larger for hemorrhagic stroke and smaller for ischemic stroke following correction for biases. In this cohort study, infertility treatment was associated with an increased risk of stroke-related hospitalization within 12 months of delivery; this risk was evident as early as 30 days after delivery. Timely follow-up in the immediate days post partum and continued long-term follow-up should be considered to mitigate stroke risk.

Indecent proposal: $5,000 is not "reasonable compensation" for oocyte donors

Sauer MV, 1999 · Fertil Steril

There is a growing threat to the practice of oocyte donation in the United States and all of us should take careful notice. This threat is posed by the escalating fees paid to young women for providing these services. I was shocked by the decision of St. Barnabas Medical Center in Livingston, New Jersey to double the compensation from the community standard of $2,500 to a startling $5,000 per cycle. These new fees were aggressively advertised throughout New Jersey and Manhattan in strategic periodicals, newspapers, and magazines. I was even more dismayed to see physicians and “ethicists” justifying the increase to the media (1) stating “there is nothing inherently wrong with bidding for human eggs.” For years, I have advocated compensation to oocyte donors based upon time, effort, and risk of involvement. I have addressed this topic at speaking engagements and in position papers, typically defending the belief that physicians are capable of responsible restraint (2, 3). However, I have been increasingly concerned over the encroachment upon the traditional practice by both commercial enterprises and physician-led groups who have inflated the cost of donor compensation 500% in the past decade. In most countries it is illegal to provide any compensation for oocyte donors. Many believe payment is inappropriate and many more agree that excessive compensation is ethically unacceptable, since it potentially exploits or even coerces young women to participate. Even if one considers the time spent traveling to the local office and waiting for an ultrasound exam to be “work,” donors now will be earning in excess of $300 per hour. I find it hard to believe that anyone thinks this “reasonable compensation” according to the recommendations of the Ethics Committee of the American Society for Reproductive Medicine (4). If we are truly not guilty of “pimping for patients” (5) and if donors are not “selling eggs,” then we cannot justify another doubling of the compensation. I believe this is a flagrant violation of the Ethical Considerations of Assisted Reproductive Technologies issued in 1994 (4). What is most disappointing is that this violation comes from a highly respected group led by physicians held in esteem within our subspecialty, who stated in The New York Times “I’m not sure $5,000 is enough.” (1) I would ask them, “How much is enough?” Where does this stop and at what price to our patients and our profession? Inevitably, all of us will be forced to raise our compensation rates to meet this challenge. Most importantly, and most unfortunately, these expenses will have to be passed on directly to our patients, who are already spending considerable sums of money to seek this procedure. I have always opposed government regulation and intervention, and I have often taken a public stand in defending our right to administer our own practices. However, for the first time in my career I am rethinking my position. If physicians are forced to drastically modify their practices to keep pace with commercial ventures or to compete with doctors whose modus operandi is “what the market will bear,” an approach to medicine so flagrantly greedy as to threaten the existence of the field, then I do believe it is time for regulation. These are truly sad events, and if we stand by and allow these changes to become standard operating procedure then we as professionals deserve the public criticism that will inevitably follow.

Motherhood at any age? Egg donation was not intended for everyone

Sauer MV, 1998 · Fertil Steril

Comparison between different routes of progesterone administration as luteal phase support in infertility treatments

Tavaniotou A et al., 2000 · Hum Reprod Update

Different routes of natural progesterone supplementation have been tried as luteal phase support in infertility treatments. Orally administered progesterone is rapidly metabolized in the gastrointestinal tract and its use has proved to be inferior to i.m. and vaginal routes. Progesterone i.m. achieves serum progesterone values that are within the range of luteal phase and results in sufficient secretory transformation of the endometrium and satisfactory pregnancy rates. The comparison between i.m. and vaginal progesterone has led to controversial results as regards the superiority of one or the other in inducing secretory endometrial transformation. However, there is increasing evidence in the literature to favour the use of vaginal progesterone. Vaginally administered progesterone achieves adequate endometrial secretory transformation but its pharmacokinetic properties are greatly dependent on the formulation used. After vaginal progesterone application, discrepancies have been detected between serum progesterone values and histological endometrial features. Vaginally administered progesterone results in adequate secretory endometrial transformation, despite serum progesterone values lower than those observed after i.m. administration, even if they are lower than those observed during the luteal phase of the natural cycle. This discrepancy is indicative of the first uterine pass effect and therefore of a better bioavailability of progesterone in the uterus, with minimal systematic undesirable effects.

A prospective randomized study comparing intramuscular progesterone and 17alpha-hydroxyprogesterone caproate in patients undergoing in vitro fertilization-embryo transfer cycles

Costabile L et al., 2001 · Fertil Steril

To compare the effectiveness of i.m. P and 17alpha-hydroxyprogesterone caproate (17-HPC) for luteal phase support, in patients undergoing IVF-ET cycles. Prospective, randomized study. Patients undergoing IVF-ET in our Centers. PATIENT(S): The inclusion criteria were the use of GnRH down-regulation and aged <40 years. INTERVENTION(S): A total of 300 cycles were randomly treated with either 17-HPC (341 mg every 3 days) or P (50 mg daily). MAIN OUTCOME MEASURE(S): The outcomes of IVF in both study groups were evaluated for biochemical pregnancy, miscarriage, clinical pregnancy, and ongoing pregnancy. RESULT(S): No difference was found in the main outcome parameters considered. CONCLUSION(S): Although the results of the study encourage the use of 17-HPC for luteal phase support in patients undergoing IVF-ET program, more studies are necessary to support the hypothesis that it can replace i.m. P-in-oil.

Oral versus intramuscular progesterone for in vitro fertilization: a prospective randomized study

Licciardi FL et al., 1999 · Fertil Steril

To evaluate the efficacy of oral micronized progesterone compared with IM progesterone in oil for luteal support in patients undergoing IVF who are treated with a GnRH agonist. Randomized prospective clinical trial. University-based IVF center. PATIENT(S): Women <40 years of age who were undergoing IVF with luteal GnRH pituitary down-regulation. INTERVENTION(S): Patients were randomized to receive either oral micronized progesterone (200 mg three times daily) or IM progesterone (50 mg daily). MAIN OUTCOME MEASURE(S): Progesterone levels at standardized days 21 and 28, and pregnancy and embryo implantation rates. RESULT(S): Day 21 progesterone levels were 77.6+/-13.2 ng/mL in the IM group and 81.5+/-16.2 ng/mL in the oral group. Day 28 progesterone levels were 76.3+/-15.0 ng/mL in the IM group and 53.6+/-10.1 ng/mL in the oral group. The clinical pregnancy rates were 57.9% and 45.8% for the IM and oral groups, respectively. The implantation rate per embryo was significantly higher in the IM group (40.9%) than in the oral group (18.1%). CONCLUSION(S): When used according to our protocols, oral progesterone and IM progesterone result in comparable levels of circulating progesterone. However, oral progesterone results in a reduced implantation rate per embryo.

The efficacy of progesterone in achieving successful pregnancy: I. Prophylactic use during luteal phase in anovulatory women

Check JH et al., 1987 · Int J Fertil

We have previously shown that prophylactic supplementation of progesterone beginning in the luteal phase of patients treated with human menopausal gonadotropins (hMG) could reduce the risk of spontaneous abortions. The present study was initiated with 100 patients to evaluate the efficacy of a new progesterone therapeutic regime in patients requiring either hMG or clomiphene citrate. A significantly decreased risk of spontaneous abortion (6% vs. 28%) was seen in 50 patients prophylactically treated with progesterone as compared with 50 control patients. The progesterone regimen was then tried on 566 consecutive patients who were treated and conceived with hMG or clomiphene citrate, and approximately the same risk (6.2% by 20 weeks) was found. This incidence of spontaneous abortion is even less than the accepted risk for the general population.