LH supplementation in IVF: human nature, politics, and elephants in the room.

Luteinizing hormone (LH) is present throughout the natural follicular phase. However, the debate is still not settled on whether LH is needed during ovarian stimulation in IVF. This commentary looks at the evolution of this debate, mentioning three elephants in the room that were ignored by the Pharma industry, professional organizations, and clinicians alike: 1. The different endocrinology between the long agonist and the antagonist protocols. 2. The fixed dose of the two most widely commercially available antagonist preparations, namely cetrorelix and ganirelix. 3. The fact that most research in this area uses population-based criteria, ignoring endocrine parameters. Individual genetics of the LH receptor gene may also serve to individualize LH needs during stimulation; however, the jury is still out regarding this approach. CONCLUSIONS: Individual endocrine and genetics parameters may shed meaningful light on the question of LH supplemental during ovarian stimulation.

Monitoring of controlled ovarian stimulation in IVF.

Since the inception of in vitro fertilization (IVF), monitoring of controlled ovarian stimulation (COS) has traditionally involved numerous appointments for ultrasound and laboratory testing to guide medication use and dosing, determine trigger timing, and allow for measures to reduce the risk of ovarian hyperstimulation syndrome (OHSS). Recent advances in the field of assisted reproductive technology (ART) have called into question the timing and frequency of COS monitoring appointments, as discussed in this commentary.

The DIY IVF cycle-harnessing the power of deeptech to bring ART to the masses.

The emergence of telehealth including telemedicine, at-home testing, and mobile health applications has enabled patients to self-manage their reproductive care, especially during the COVID-19 pandemic. Reproduction is rapidly changing and embracing deeptech initiatives that can improve outcomes and facilitate personalized fertility solutions in the near future. This so-called DIY IVF informed by deeptech and moderated by femtech not only holds a tremendous amount of promise, but also challenges and possible pitfalls. This review discusses the current status of deeptech and femtech for IVF care in a post-Roe v. Wade environment.

Looking with new eyes: advanced microscopy and artificial intelligence in reproductive medicine.

Microscopy has long played a pivotal role in the field of assisted reproductive technology (ART). The advent of artificial intelligence (AI) has opened the door for new approaches to sperm and oocyte assessment and selection, with the potential for improved ART outcomes.

Use of pulsatile gonadotropin-releasing hormone (GnRH) in patients with functional hypothalamic amenorrhea (FHA) results in monofollicular ovulation and high cumulative live birth rates: a 25-year cohort.

PURPOSE: To analyze outcomes of pulsatile administration of gonadotropin-releasing hormone (GnRH) in infertile women diagnosed with functional hypothalamic amenorrhea (FHA). METHODS: A single-center retrospective cohort study was conducted from 1996 to 2020. Sixty-six patients with the diagnosis FHA that underwent therapy using the pulsatile GnRH pump for conception were included and analyzed. The primary outcome was the live birth rate (LBR). Secondary outcomes were the number of dominant follicles, ovulation rate, biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), miscarriage rate, and multiple pregnancy rate. A matched control group was selected to compare the birth weight of newborn children. RESULTS: During the study period, 66 patients with FHA underwent 82 treatments (14 of 66 patients had more than one treatment) and a total of 212 cycles (ovulation induction attempts) using pulsatile GnRH. The LBR per treatment was 65.9%. The ovulation rate per cycle was 96%, and monofollicular ovulation was observed in 75% of cycles. The BPR per treatment was 80.5%, and the cumulative CPR per treatment was 74.4%. The miscarriage rate was 11.5%. One dizygotic twin pregnancy was observed (1.6%). Average newborn birth weight (NBW) from patients with FHA was comparable to the control group. CONCLUSION(S): In patients with FHA, excellent pregnancy rates were achieved using the subcutaneous GnRH pump. The high cumulative LBR with normal NBW as well as low rates of multiple gestation indicate that the pulsatile GnRH pump represents a safer and more physiologic alternative to ovulation induction with injectable gonadotropins. TRIAL REGISTRATION: Ethics Committee Northwest and Central Switzerland (Ethikkommission Nordwest- und Zentralschweiz - EKNZ) - Project-ID 2020-01612.

Protecting life in a time of war.

Despite centuries of lessons from history, war endures. Across Earth, during nearly every year from the beginning of the twentieth century to present day, over 30 wars have been fought resulting in 187 million casualties, excluding the most recent conflict, which is the impetus for this essay (Timeline of 20th and 21st century wars). We are, sadly, a war-mongering people. The word "war" word infiltrates our vernacular, e.g., the war on poverty, on drugs, on cancer, on COVID, and, apropos, on terror. How did rational approaches to disagreement and conflict evade the world's progress? Reproductive physicians and scientists are dedicated to safeguard lives and build families. Violence is antithetical to our mission as professionals, and moral integrity as humans. We are deeply concerned for, and stand in unity with, our Ukrainian colleagues-the embryologists, scientists, OBGYN and REI physicians, infertility patients, and all people under siege. Reproductive health services for Ukrainians (as with many other war-torn regions) have collapsed. Deeply disturbing reports have emerged that cite civilian hospitals (including maternity centers) being targeted. Liquid nitrogen supplies are scarce. Pregnant mothers and gestational carriers are at emergent risk of delivering in extremely harsh conditions, cold underground bunkers and refugee queues.

Triggering change in stimulation protocols: a matter of oocyte maturation and beyond.

Since the birth of Louise Brown, in vitro fertilization (IVF) stimulation protocols have evolved significantly. One particular area of focus has been the process of final oocyte maturation, during which the oocyte gains competence to support fertilization and early embryonic development up to implantation. The field of human assisted reproductive technology (ART) is witnessing increased utilization of GnRH agonists (GnRHa) as trigger agents, in addition to or instead of the traditionally used human chorionic gonadotropin (hCG). Future translational studies will reveal whether oocyte developmental competence, as reflected in live birth outcomes, are not only non-inferior, but also superior with the use of GnRHa as a trigger for both nuclear and cytoplasmic oocyte maturation.

ICSI for non-male factor: do we practice what we preach?

Since its introduction in 1992, intracytoplasmic sperm injection (ICSI) has revolutionized the treatment of infertility due to severe male factor. Over the last three decades, the use of ICSI for non-male factor has increased dramatically, despite guidelines to the contrary from professional societies. Excessive utilization of ICSI is primarily due to an irrational fear of total fertilization failure, which is at odds with rational evidence to support its use.

Obesity and IVF: weighing in on the evidence.

Obesity is associated with serious health risks, and its rising prevalence represents a growing public health emergency. Ongoing research into the association of obesity and assisted reproductive technology (ART) outcomes aims to disentangle selective detrimental effects of obesity on the oocyte and the endometrium. More translational studies involving women with severe obesity and in the third-party reproduction setting will help improve the standard of care in the provision of ART services for obese patients.

Artificial intelligence-the future is now.

The pros and cons of artificial intelligence in assisted reproductive technology are presented.

Frozen-thawed embryo transfers: time to adopt a more "natural" approach?

The increasing use of frozen-thawed embryo transfer (FET) cycles has magnified the focus on endometrial preparation protocols in assisted reproduction. Emerging evidence suggests that natural cycle (NC) FETs are associated with improved outcomes, and that providers should consider increasing the utilization of NC FET at the expense of the currently favored artificial cycle (AC) FET as primary method for endometrial preparation.

Social media in ART-#power or #peril?

The impact of social media on the practice of ART is rapidly increasing, heralding great promise, but also significant risks. Since social media are likely here to stay, providers should familiarize themselves with this rapidly emerging phenomenon and decide how to best use it for their practice.

Antenatal antioxidants to avert autism?

Paternally derived de novo mutations (DNMs) caused by oxidative stress (OS) have been implicated in the development of autism spectrum disorders (ASDs). Whether preconception antioxidant supplementation can reduce the incidence of ASDs by reducing OS is an area of uncertainty and potentially important future scientific investigation.

Local privileges not universal rights: geographic variations in the science and clinical practice of reproductive medicine.

Based on personal experience in the science and clinical practice of reproductive medicine in different settings, enormous variations are highlighted, demonstrating that freedom of research and clinical practice in reproductive medicine is a local privilege, not a universal right.

Impact of Zika virus for infertility specialists: current literature, guidelines, and resources.

In the past 2 years, Zika virus has emerged from obscurity onto the world stage-traversing and transcending clinical specialties, basic science disciplines, and public health efforts. The spread of Zika virus has serious implications for the specialty of reproductive endocrinology and infertility. Our patients, practices, and labs-worldwide and specifically in the USA-have been impacted by this teratogenic, sexually transmitted, largely asymptomatic virus. While the World Health Organization's Public Emergency of International Concern designation has lapsed as major epidemics have subsided and understanding of risks is in part clarified, the acute and long-term threat to pregnant patients is not over. The risk of wider spread in the USA is not insignificant, the subtler and long-ranging consequences beyond microcephaly are not fully known, large geographic areas of risk still contain naïve populations, and whether Zika will continue to be an intermittent risk in endemic areas is uncertain. Staying up to date with the burgeoning research on Zika virus is an important objective for the infertility specialist. Here, we review in detail the most relevant recent developments, discuss applicable guidelines, and propose strategies for contributing to a reduction in the risk and burden of Zika virus.

The dilemma of counseling patients about poor prognosis: live birth after IVF with autologous oocytes in a 43-year-old woman with FSH levels above 30 mIU/mL.

Providing reasonable expectations to patients with diminished ovarian reserve prior to attempting pregnancy through in vitro fertilization (IVF) is one of the most challenging aspects of fertility care. In some instances, advice from the clinician to pursue more effective treatment, such as donor oocytes, may not be acceptable to the patient. In this case report, a patient is presented who represents a poor prognosis candidate for IVF treatment. She was 43 years old with six prior failed IVF cycles and repetitive basal FSH values above 30 mIU/mL. Presented are the challenges in patient counseling and decision making. In her seventh IVF cycle, which she was strongly counseled against pursuing, the patient experienced the desired outcome of live birth. Increasing reports are emerging of live birth using autologous oocytes among women of advanced reproductive age. These instances, as well as the case of our patient, raise issues commonly encountered in patient counseling in poor prognosis patients. This discussion should include an emphasis on patient goals as well as an acknowledgement that no test for ovarian reserve has a 100% positive predictive value.

Lifestyle factors associated with histologically derived human ovarian non-growing follicle count in reproductive age women.

STUDY QUESTION: Are lifestyle factors (smoking, BMI, alcohol use and oral contraceptive pill use) associated with the human ovarian reserve as determined by the total ovarian non-growing follicle number? SUMMARY ANSWER: Light to moderate alcohol use was significantly associated with greater ovarian non-growing follicle (NGF) count, whereas other lifestyle factors were not significantly related. WHAT IS KNOWN ALREADY: A single previous investigation has suggested that smoking and alcohol use are associated with lower ovarian follicle density. However, this investigation utilized follicle density as the outcome of interest rather than the estimated total ovarian NGF count. STUDY DESIGN, SIZE, DURATION: This cross-sectional investigation included a convenience sample of premenopausal women from two different academic sites, the University of Washington (n = 37, from 1999-2004) and the University of Oklahoma (n = 73, from 2004-2013), undergoing incidental oophorectomy at the time of hysterectomy (total n = 110, age range 21-52 years). PARTICIPANTS/MATERIALS, SETTING, METHODS: Prior to undergoing oophorectomy, participants completed detailed questionnaires regarding lifestyle exposures. Following surgery, total ovarian NGF counts were determined with systematic random sampling rules and a validated fractionator/optical dissector technique. Associations between lifestyle factors and log-transformed ovarian follicle counts were determined using multivariable linear regression. MAIN RESULTS AND THE ROLE OF CHANCE: After controlling for age, BMI, oral contraceptive pill (OCP) use, tobacco use and site of collection, cumulative alcohol use (measured in alcoholic drinks per day multiplied by years of drinking) was associated with ovarian NGF count. Women reporting light (>0 to <1 drink-years) and moderate (1-3 drink-years) alcohol use had greater NGF counts (ß = 0.75, P = 0.04, and ß = 1.00, P = 0.03; light and moderate use, respectively) as compared with non-users. Neither heavier alcohol use (>3 drink-years), BMI, OCP use, nor tobacco use were significantly associated with the ovarian NGF count. Similar patterns of association with moderate cumulative alcohol use were observed when evaluating associations with pre-antral follicles and total follicle counts. LIMITATIONS, REASONS FOR CAUTION: All participants in this convenience sample had a benign indication for hysterectomy, and therefore may not be broadly representative of the population without such an indication. Additionally, lifestyle factors were self-reported, and the sample size of the present investigation limits our ability to detect associations of smaller magnitude. WIDER IMPLICATIONS OF THE FINDINGS: While our findings are in disagreement with a single investigation that utilized human follicle density as the outcome of interest, they are consistent with many studies investigating the relationship between lifestyle factors and the age of spontaneous menopause. Furthermore, they suggest a mechanism that does not involve accelerated follicular atresia to explain the association between smoking and an earlier age of menopause. STUDY FUNDING/COMPETING INTERESTS: This investigation was funded by NIA R29-HD37360-04 (N.A.K.) and OCAST HR04-115 (K.R.H.) and by the National Institute of General Medical Sciences, Grant 1 U54GM104938 (J.D.P.). There is no conflict of interest.