Karyotypic abnormalities and Y chromosome microdeletions: How do these impact in vitro fertilization outcomes, and how common are they in the modern in vitro fertilization practice?

OBJECTIVE: To examine the outcomes of in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) in couples in whom the male partner has a karyotypic abnormality or Y chromosome microdeletion (YCM). DESIGN: Retrospective cohort. SETTING: Single infertility center. PATIENTS: Couples treated with IVF-ICSI from January 2014 to April 2019 with male factor infertility, sperm concentration of <5 × 106 sperm/mL, and results for karyotype and/or YCM panel. INTERVENTIONS: In vitro fertilization with intracytoplasmic sperm injection. MAIN OUTCOME MEASURES: In couples in whom the male partner had a karyotypic abnormality or YCM: live birth rate/ongoing pregnancy rate, lack of partner sperm for fertilization, complete fertilization failure, cycle cancellation, and no embryos for transfer. The prevalence of karyotypic abnormalities and YCMs in the IVF population was calculated. RESULTS: The live birth rate/ongoing pregnancy rate for those using partner sperm was 51.4% per transfer. However, 8.5% of cycles that intended to use partner sperm and 22.2% of cycles that intended to use surgically extracted partner sperm had no sperm available. Of cycles that created embryos with partner sperm, 12.5% had no embryo to transfer. The prevalence of karyotypic abnormalities was similar to previous reports (6.0%), while that of YCMs was lower (4.4%). Azoospermia factor a and b mutations were not represented in this population. CONCLUSIONS: It is reasonable to attempt IVF-ICSI with partner sperm in patients with genetic causes of male infertility. Patients should be counseled regarding the possibility of no sperm being available from the male partner, poor/failed fertilization, and genetic implications for potential offspring. Contingency plans, including IVF with donor sperm backup or oocyte cryopreservation, need to be made for these scenarios.

Does ovarian stimulation benefit ovulatory women undergoing therapeutic donor insemination?

OBJECTIVE: To compare clinical and ongoing pregnancy after natural cycle (NC) intrauterine insemination (IUI) versus ovarian stimulation (OS) IUI in ovulatory women undergoing therapeutic donor insemination (TDI). DESIGN: Retrospective cohort. SETTING: Single infertility center. PATIENT(S): A total of 76,643 IUI cycles in patients treated with intrauterine insemination were examined. Women undergoing TDI in the absence of diagnosed female factor infertility were included. INTERVENTION(S): NC TDI or OS TDI with either clomiphene citrate or letrozole. MAIN OUTCOME MEASURE(S): Clinical and ongoing pregnancies were analyzed by generalized estimating equations adjusting for age, body mass index, total motile sperm at time of insemination and cycle number. Ongoing multiple gestations were examined as a secondary outcome. RESULT(S): Six thousand one hundred ninety-two TDI cycles from 2,343 patients (711 patients without repeated IUI cycles) met inclusion criteria and were available for analysis (3,837 NC and 2,355 OS). There was no difference in mean age between the two groups (NC, 34.2 years vs. OS, 34.3 years). Probability of clinical and ongoing pregnancy was higher in the OS cohort compared with the NC cohort (OS, 22.4% vs. NC, 18.7% and OS, 15.4% vs. NC, 14.9%, respectively). However, OS significantly increased ongoing multiple gestations (OS, 10.8% vs. NC, 2.4%). CONCLUSION(S): Ovarian stimulation in TDI cycles resulted in a <4% increase in clinical and <1% increase in ongoing pregnancy, and more than fourfold increase in ongoing multiple gestations. Natural cycle IUI should be considered as a first-line treatment for ovulatory women who need donor insemination.

Polycystic Ovary Syndrome: Menopause and Malignancy.

Polycystic ovary syndrome (PCOS) has been extensively studied in reproductive-aged women. However, accumulating research shows that PCOS can have lifelong effects on multiple aspects of women's health. PCOS can affect the onset and course of menopause and cardiovascular health in perimenopausal and postmenopausal patients. Moreover, PCOS may increase a woman's risk for both gynecologic and nongynecologic malignancies. When treating older PCOS patients, physicians should be cognizant of the syndrome's long-term effects and consider the unique needs of these women.

The Lion King of ovulation induction.

Melvin Taymor's daughter, Julie Taymor, directed the musical version of The Lion King, which won six Tony Awards. Known for her revolutionary staging, she became the first woman to be awarded a Tony for Best Direction of a Musical.

Ovarian vein sampling, and serum and urine testosterone monitoring in ovarian Leydig cell tumors: A report of two cases.

BACKGROUND: Ovarian Leydig cell tumors are rare, testosterone-producing tumors that pose diagnostic challenges. CASES: A 36-year-old woman presented with 10 years of amenorrhea, facial hair growth and clitoromegaly. A 59-year-old woman presented after 2 years of voice deepening and terminal hair growth. Testosterone concentrations were elevated for both patients; however, imaging failed to identify ovarian or adrenal pathology. For the first patient, selective ovarian venous sampling was performed with results suggesting right ovarian testosterone production. Right ovarian Leydig cell tumors were found in both patients after salpingo-oophorectomy. Testosterone levels immediately declined following tumor removal. CONCLUSION: Additional diagnostic modalities, such as ovarian venous sampling, should be considered when the etiology of hyperandrogenism cannot be identified through lab work or imaging. In addition, sequential post-operative testosterone levels in serum or urine can help confirm adequate removal of the ovarian tumor.

SARS-CoV-2 found in semen.

With a novel coronavirus comes novel unknowns. One such unknown was whether or not the SARS-CoV-2 virus could be detected in semen. A recent report demonstrated the presence of the virus in semen, which raises additional questions.

Fertility preservation in an oncology patient who presented with positive human chorionic gonadotropin.

OBJECTIVE: To report the case of a woman who presented for fertility preservation before breast cancer treatment who was found to be pregnant with an undesired pregnancy. DESIGN: Case report. SETTING: Single infertility practice. PATIENT: A 28-year-old woman with a new diagnosis of grade 3 invasive ductal carcinoma of the breast was planning to undergo oocyte cryopreservation and was found to be pregnant with an undesired pregnancy. She underwent a medical termination at a gestational age of 5 weeks 4 days. Neither the patient nor her oncology team wished to delay treatment more than was necessary. The physician and patient decided to initiate controlled ovarian hyperstimulation (COH) before her human chorionic gonadotropin (hCG) returned to normal. INTERVENTIONS: COH in the setting of a positive quantitative hCG. MAIN OUTCOME MEASURES: Number of metaphase II (MII) oocytes cryopreserved; doses of Gonal-F and Menopur; serum E2, follicle-stimulating hormone, luteinizing hormone, hCG levels. RESULTS: COH began 7 days after passing the products of conception. Baseline labs demonstrated hCG at 222 mIU/mL, follicle-stimulating hormone at <0.10 mIU/mL, luteinizing hormone at <1.10 mIU/mL, and E2 at 147 pg/mL. She was started on an antagonist protocol with the use of 150 IU Gonal F and 75 IU Menopur. She was triggered on stimulation day 14 with 5,000 U hCG, and her peak E2 was 5,924 pg/mL. She ultimately had 18 oocytes retrieved, 12 of which were MII, one MI, and five germinal vesicle. All were vitrified. CONCLUSIONS: COH can be achieved in the setting of low positive hCG levels with subsequent successful oocyte maturation. The threshold for hCG trigger to be ineffective in the setting of a positive hCG has yet to be determined.

Fertility preservation before hematopoetic stem cell transplantation: a case series of women with GATA binding protein 2 deficiency, dedicator of cytokinesis 8 deficiency, and sickle cell disease.

OBJECTIVE: To describe fertility characteristics, outcomes of oocyte cryopreservation cycles, and safety of ovarian stimulation in patients with GATA binding protein 2 (GATA2) deficiency, dedicator of cytokinesis 8 (DOCK8) deficiency, and sickle cell disease (SCD) preparing for hematopoetic stem cell transplantation (HSCT). DESIGN: Retrospective case series. SETTING: The National Institutes of Health. PATIENTS: Female patients with GATA2 deficiency, DOCK8 deficiency, and SCD aged between 13 and 38 years. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Demographic and ovarian reserve parameters, stimulation outcomes, and adverse event occurrences were collected through chart review. Descriptive statistics were used to identify trends within disease subcategories. RESULTS: Twenty-one women with GATA2 deficiency, DOCK8 deficiency, and SCD underwent fertility preservation prior to HSCT. Patients with DOCK8 deficiency had the lowest mean age (16.5 years old) and antimüllerian hormone (0.85 ng/mL). Patients with GATA2 deficiency had the highest antral follicle count and antimüllerian hormone (25.77 and 5.07 ng/mL, respectively). Baseline follicle-stimulating hormone, luteinizing hormone, and estradiol were comparable between the cohorts. The duration of stimulation was similar (10.43 to 11.25 days) across all groups. Comparable peak estradiol levels were achieved across the cohorts. Patients with SCD had the highest mature (MII) oocyte yield (10.71). Three patients experienced complications related to stimulation: pain crisis in a patient with SCD, pulmonary embolism, and zero oocytes cryopreserved in a patient with GATA2 deficiency. CONCLUSIONS: This study offers insight into controlled ovarian stimulation in patients with these conditions prior to HSCT. Oocyte cryopreservation can be performed successfully, although adverse events must be considered. Following the outcomes of gamete use in this cohort will serve to further our knowledge of the true reproductive potential of this population.

A different time for tubal surgery.

"An object in motion tends to remain in motion along a straight line unless acted upon by an outside force." -Isaac Newton.

Theory of relativity of progress.

"All progress is precarious, and the solution of one problem brings us face to face with another problem." -Martin Luther King, Jr.

Phenotypic variations in X chromosome mutations: Two case reports.

Turner syndrome (TS) affects 1 in 2500 females. Monosomy X is the most common etiology, classically presenting with hypoestrogenemia and short stature. We present two cases of partial X chromosome deletions that do not reflect the typical phenotype of TS. Patient 1 presented at age 17 with primary amenorrhea, cognitive delay and tall stature. Patient 2 presented at age 16 with primary amenorrhea, normal intelligence and average stature. Patient 1's karyotype revealed isodicentric X chromosome [46 X, idic(X)(q21)]. Patient 2's karyotype revealed [46 X,del(X)(q13.3)]. The stature of these patients was not affected. Estrogen therapy was required to provide secondary sexual changes promote bone health. Advances in technology and reproductive health provide an opportunity to make more specific recommendations for patients previously mistakenly diagnosed with TS.

Facts often fail to overcome preconceived notions.

"Study the past if you would define the future." - Confucius.

Old insights, same questions.

The thing that hath been, it is that which shall be; and that which is done is that which shall be done: and there is no new thing under the sun. -Ecclesiastes 1:9, King James Bible.

Developmental Origins of Health and Disease: The History of the Barker Hypothesis and Assisted Reproductive Technology.

Since Barker's publication of "The fetal and infant origins of adult disease" in 1990, significant emphasis has been placed on the intrauterine environment and its effect on adult disease. Historical events such as the Dutch Famine and the 1918 Flu Pandemic have provided organic data about the epigenetic changes that can result from famine, infection, and stress. Mechanisms that allow for intrauterine survival may predispose to adult disease states when the fetus enters a world of abundance. As the field of in vitro fertilization (IVF) has developed and evolved, little attention has been paid to subtle yet significant differences in IVF offspring. Offspring of assisted reproductive technology (ART) have been reported to have higher rates of preterm birth, abnormal fetal size, and birth defects. It is clear that epigenetic modifications may begin as early as pre-pregnancy. These differences are likely not attributable to one factor in the IVF process. Each variable likely plays a subtle role in the epigenetic manipulation of the embryo. Thus, moving forward, physicians should practice with heightened determination to follow the long-term outcomes of the offspring of ART in an effort to further modify and perfect the field.

Utilization of fertility treatment and reproductive choices by lesbian couples.

OBJECTIVE: To describe intentions and outcomes of lesbian couples requesting reproductive assistance; and report number of cycles needed to achieve a live birth. DESIGN: Retrospective chart review. SETTING: University-based fertility center. PATIENT(S): A total of 306 lesbian couples who sought reproductive assistance between 2004 and 2015. INTERVENTION(S): Intrauterine insemination or IVF using donor sperm. MAIN OUTCOME MEASURE(S): Mean age, relationship status, family size, preconception goals, conception attempts, number of cycles to achieve a live birth. RESULT(S): Preconception plans were available for 233 couples: 76.4% planned for one partner to conceive and carry (single partner conception); 23.6% planned for both partners to eventually conceive and carry (dual partner conception). Of 306 couples who presented, 85.1% attempted single partner conception, and 68% of these achieved a live birth. Dual partner conception was attempted by 14.9% of couples, and 88.9% achieved a live birth. Of those who conceived with IUI, a mean (±SD) of 3 ± 1.1 cycles were completed. Of those who conceived with IVF, a mean of 6 ± 1.4 IUI and 1.7 ± 0.3 IVF cycles were completed. CONCLUSION(S): Lesbian couples may improve their likelihood of a live birth if both partners attempt conception. Further studies are needed to understand why one-fifth of patients did not pursue treatment.