Tubal Ectopic Pregnancy with Undetectable Initial Serum ß-Human Chorionic Gonadotropin Level.

We present a case of a tubal ectopic pregnancy (EP) in a patient with an initially undetectable serum ß-human chorionic gonadotropin (ß-hCG) level. A 33-year-old woman in a same-sex relationship underwent timed donor intrauterine insemination. Her serum ß-hCG level was <5 mIU/mL 14 days after the intrauterine insemination. She reported menstrual bleeding 3 days after her negative pregnancy test and returned to the office 10 days later to begin a new treatment cycle. Her serum levels of estradiol, progesterone, and ß-hCG were 119 pg/mL, 6.1 ng/mL and 1157 mIU/mL, respectively. Transvaginal ultrasonography did not show an intrauterine pregnancy. Her ß-hCG level increased to 1420 mIU/mL the next day. She was diagnosed with a pregnancy of unknown location and treated with methotrexate. Her ß-hCG levels continued to increase despite 3 methotrexate doses, necessitating laparoscopy. The diagnostic laparoscopy demonstrated approximately 100 mL of hemoperitoneum in the posterior cul-de-sac with an intact right fallopian tube that was dilated at its distal end by the EP. A total right salpingectomy was performed. Her ß-hCG level was <5 mIU/mL 3 weeks later. The current case supports that although rare, an undetectable serum ß-hCG level does not completely rule out the diagnosis of an EP.

Self-reported physical health status of donor sperm-conceived adults.

Donor-conceived neonates have poorer birth outcomes, including low birth weight and preterm delivery that are associated with poorer long-term health in adulthood through the developmental origins of health and disease (DOHaD) theory. The aim of this study was to conduct the first investigation of the adult health outcomes of donor-conceived people. An online health survey was completed by 272 donor sperm-conceived adults and 877 spontaneously conceived adults from around the world. Donor and spontaneously conceived groups were matched for age, sex, height, smoking, alcohol consumption, exercise, own fertility and maternal smoking. Donor sperm-conceived adults had significantly higher reports of being diagnosed with type 1 diabetes (P = 0.031), thyroid disease (P = 0.031), acute bronchitis (P = 0.008), environmental allergies (P = 0.046), sleep apnoea (P = 0.037) and having ear tubes/grommets surgically implanted (P = 0.046). This is the first study to investigate the health outcomes of adult donor sperm-conceived people. Donor sperm-conceived adults self-reported elevated frequencies of various health conditions. The outcomes are consistent with birth defect data from donor sperm treatment and are consistent with the DOHaD linking perturbed early growth and chronic disease in adulthood.

The incidence of hypertensive disorders of pregnancy following sperm donation in IVF: an Australian state-wide retrospective cohort study.

STUDY QUESTION: Does IVF using donor sperm increase the risk of hypertensive disorders of pregnancy and fetal growth restriction (FGR)? SUMMARY ANSWER: IVF conceptions arising from sperm donation are not associated with an increased risk of hypertensive disorders of pregnancy or FGR. WHAT IS KNOWN ALREADY: It has been hypothesized that the absence of prior exposure to factors within the paternal ejaculate increases the risk of preeclampsia and FGR among nulliparous women or women with a new partner-the concept of 'primipaternity'. It remains unclear which element of the ejaculate is responsible: the sperm cell or the constituents of seminal fluid. IVF pregnancies arising from donor sperm where the seminal fluid is absent provide a unique opportunity to test the theory of primipaternity and the relative contribution of the sperm cell. Pregnancies conceived via artificial reproductive technology are at increased risk of preeclampsia and FGR. STUDY DESIGN, SIZE, DURATION: Theories about the development of preeclampsia and the relative contribution of spermatic factors were explored by comparing the risk of hypertensive disorders of pregnancy and FGR among IVF pregnancies conceived with autologous gametes (own eggs and partner sperm) and those conceived with donor sperm, donor egg (and partner sperm) and donor embryo. To do this, we performed a retrospective cohort analysis of pregnancy outcomes among singleton pregnancies (n = 15 443) conceived through fertility clinics within Australia between 2009 and 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: All pregnancies resulting in a singleton pregnancy delivering after 20 weeks' gestation were included. The cohort was divided into donor sperm, donor egg and donor embryo (where both gametes came from a donor to create an embryo, or in a surrogate pregnancy) groups. We also compared the data with a control group, defined as IVF-conceived pregnancies from autologous cycles. A multivariable regression model was used to calculate an adjusted odds ratio (aOR). MAIN RESULTS AND THE ROLE OF CHANCE: The final cohort contained 1435, 578 and 239 pregnancies conceived by donor sperm, donor egg and donor embryo, respectively, and 13 191 controls. There were a very small number of women lost to follow-up (31 women; 0.2% of total cohort). Compared to control pregnancies, there was no increase in the risk of hypertensive disorders among pregnancies conceived via donor sperm (aOR 0.94; 95% CI 0.73-1.21). Subgroup analysis was performed for a cohort where parity was known (n = 4551), and of these, 305 multigravida pregnancies were conceived via donor sperm. Among this cohort, no increased risk of preeclampsia or pregnancy-induced hypertension was found (aOR 1.18; 95% CI: 0.69-2.04) as a result of primipaternity (new sperm donor).A significantly increased risk for hypertensive disorders of pregnancy was associated with the use of donor eggs (but partner sperm; aOR 2.34; 95% CI 1.69-3.21). However, the association was no greater among pregnancies conceived with donor embryos (i.e. donated egg and sperm; aOR 2.0; 95% CI 1.25-3.17) than among the donor oocyte group. The overall incidence of FGR (defined as birthweight <10th centile) was 18%. There were no significant differences observed between donor sperm, or donor embryo pregnancies; however, egg donation was associated with a 1.5-fold increase in FGR. LIMITATIONS, REASONS FOR CAUTION: This study was limited by a lower than expected rate of hypertensive disorders of pregnancy (n = 862, 5.6%), which is contrary to the well-established increased risk among women using IVF. However, this is likely to be evenly distributed across the study groups and, therefore, unlikely to have introduced significant bias. WIDER IMPLICATIONS OF THE FINDINGS: These findings suggest that exposure to new sperm may not be implicated in the pathogenesis of preeclampsia. The mechanism of increased risk seen in conceptions arising from egg or embryo donation remains unclear. Further investigation is required to elucidate these mechanisms and, ultimately, improve pregnancy outcomes following IVF. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Australian Commonwealth Government-Graduate Research Scheme (A.K.). Salary support was provided by the National Health and Medical Research Council of Australia (S.T.), Mercy Foundation (A.L.), and the Department of Obstetrics and Gynaecology at the University of Melbourne (R.H.). There are no competing interests.

Infectious human papillomavirus virions in semen reduce clinical pregnancy rates in women undergoing intrauterine insemination.

OBJECTIVE: To study the influence of human papillomavirus (HPV) virions present in different sperm fractions of male partners of women undergoing IUI on fertility outcome. DESIGN: Prospective noninterventional multicenter study. SETTING: Inpatient hospital fertility centers. PATIENT(S): Seven hundred thirty-two infertile couples undergoing 1,753 IUI cycles with capacitated sperm. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Biochemical and clinical pregnancy rate in IUI cycles with HPV-positive or HPV-negative semen. RESULT(S): Five hundred seventy-three infertile couples undergoing 1,362 IUI cycles were enrolled. Work-up of the 1,362 sperm samples that were used for IUI generated 3,444 separate sperm fractions. Each of the sperm fractions was tested with quantitative polymerase chain reaction for 18 different HPV types (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 67, and 68). HPV prevalence in sperm was 12.5%/IUI cycle. When infectious HPV virions were detected in sperm, a significant decrease in clinical pregnancies was observed when compared with HPV-negative cycles (2.9% vs. 11.1 %/cycle). Above a ratio of 0.66 HPV virions/spermatozoon no pregnancies occurred (sensitivity 100%, specificity 32.5%). CONCLUSION(S): Women inseminated with HPV-positive sperm had 4 times fewer clinical pregnancies compared with women who had HPV-negative partners. Detection of HPV virions in sperm is associated with a negative IUI outcome and should be part of routine examination and counseling of infertile couples. EUROPEAN CLINICAL TRIALS DATABASE NUMBER: 2017-004791-56.

Ethical quandaries around expanded carrier screening in third-party reproduction.

Although current screening methods of gamete donors are capable of reducing the incidence of genetic anomalies in donor offspring below general population levels, targeted screening for a large number of conditions (expanded carrier screening or ECS) could be considered as part of the routine selection procedure for gamete donors. There are, however, important drawbacks to its practical implementation. Excluding all carriers of severe recessive monogenic pediatric disorders would disqualify virtually all donors, and other approaches negatively affect cost (and therefore access), present dilemmas in regard to disclosure of genetic findings, and/or overburden the intended parents. In all of the scenarios considered, adequate genetic counseling will be of central importance. Besides looking at benefits and drawbacks of possible ways of implementing ECS, we also examine whether a moral obligation exists to adopt ECS at all and on whose shoulders such an alleged obligation would rest: policymakers, medical staff at fertility clinics, sperm and egg banks, the intended parents? We argue that given the small risk reduction brought about by ECS, the possible negative effects of its implementation, and the absence of widespread preconception carrier screening in the general population, it is inconsistent to argue that there is a moral obligation to perform ECS in the context of donor conception. Finally, implications for the donors are discussed.

Risk of pelvic inflammatory disease after intrauterine insemination: a systematic review.

The aim of this study was to ascertain the incidence of pelvic inflammatory disease (PID) after intrauterine insemination (IUI). A systematic review was conducted using three different approaches: a search of IUI registries; a search of published meta-analyses; and a search of prospective randomized trials. Search terms were 'IUI', 'complications', 'infection' and 'PID'. Two IUI registers were identified that met the inclusion criteria, totalling 365,874 cycles, with 57 PID cases being reported. The post-IUI PID rate was 0.16/1000 (95% CI 0.2 to 0.3/1000). The frequency was higher in husband sperm cycles (0.21/1000) (28/135,839) than in donor sperm cycles (0.03/1000) (1/33,712) (P < 0.05; OR 6.95). Nineteen meta-analyses were retrieved, which included 156 trials, totalling 43,048 cycles, with no PID case being reported. Seventeen prospective clinical trials published between 2013 and 2014 were identified, totalling 4968 cycles; no PID case was reported. The reported rate of post-IUI clinical PID is low (0.16/1000), about 40% higher than reported in the general population of women during their reproductive life. No antibiotic prophylaxis should be recommended unless there is an associated risk factor.

Short-term safety evaluation of the offspring conceived by 7272 artificial insemination cycles with donor spermatozoon.

This case-control study was designed to investigate the safety of the AID technology. The health status of the offspring conceived by 1620 couples who underwent 7272 AID cycles in our Center for Reproductive Medicine between June 2006 and December 2012 was retrospectively analysed. The control group included 1018 women who naturally conceived and delivered in the same period. Twin birth rate was significantly higher in the AID group (no triplet birth) than in the control group (2.01% versus 0.39%, P < 0.01). In the AID group, Caesarean delivery was used in 1299 cases (81.65%), spontaneous vaginal delivery (18.04%) and forceps-assisted vaginal delivery (0.31%).There was no significant difference in male/female ratio of the offspring between AID and control groups (113.55 : 100 versus 113.36 : 100, P > 0.05). Compared to natural pregnancy, a pregnancy through AID resulted in higher multiple birth rate, premature delivery rate and neonatal congenital malformation rate. Increased multiple birth rate was attributable to ovulation induction, and increased rate of low-birthweight infants was related to multiplets and premature delivery. Caesarean delivery was preferred in couples who received AID treatment. The male/female ratio of the AID offspring was similar between natural pregnancy and AID pregnancy.

Processing, selecting and ritualizing: ambivalent relationships to semen.

Two articles on human immunodeficiency virus (HIV) and reproduction have recently been published in Reproductive BioMedicine Online, both describing developments that increase reproductive options for HIV-positive men. A study of a semen-processing technique used at a South African hospital found that two out of 103 processed samples tested positive for HIV DNA and none for RNA, indicating 98.1% and 100% effectiveness, respectively. The authors recommend semen processing followed by viral validation of processed sperm samples when providing assisted reproduction treatment to couples with an HIV-positive male partner. The other article reviews developments such as semen processing, antiretroviral (ARV) therapy and pre-exposure prophylaxis (PrEP), which have all reduced the risk of HIV transmission in the context of reproduction. The author also notes, however, that research on fertility in the context of HIV focuses almost exclusively on heterosexual couples, and has overlooked the links between reproduction, HIV and homosexuality. This article analyses the ambivalent role of semen - associated with both reproduction and infection - and how reproductive medicine and health care in different ways seek to 'get hold' of sperm. By taking this analytic approach, sex and parenthood can be thought of as two different but related kinds of intimacy and kinship.

Repro-sexual intersections: sperm donation, HIV prevention and the public interest in semen.

In the scientific literature on fertility and assisted reproduction, and in the corresponding area of clinical practice, increasing attention has been paid to two groups: people living with the human immunodeficiency virus (HIV) and gay men. However, research on fertility in the context of HIV focuses almost exclusively on heterosexual couples, whereas studies on non-heterosexual reproduction rarely mention HIV, despite the fact that, in many western countries, HIV prevalence among men who have sex with men is higher than ever before and men who have sex with men are the only group in which new HIV infections are on the rise. This review identifies links between reproduction, HIV and homosexuality, showing that, historically, they are closely intertwined, which has important implications for current issues facing HIV care and fertility services. Considering sex and parenthood as two different but related kinds of intimacy and kinship, the dual role semen plays in sexually transmitted infection and in assisted reproduction is discussed. The review reflects on the future of sperm donation and HIV prevention, asking whether two challenges that potentially face healthcare and medicine today - the shortage of 'high-quality' sperm and the 'surplus' of infected semen - could be addressed by a greater exchange of knowledge.

Influence of follicle rupture and uterine contractions on intrauterine insemination outcome: a new predictive model.

OBJECTIVE: To correlate the detection of follicle rupture and the number of uterine contractions per minute with the outcome of IUI and to build a predictive model for the outcome of IUI including these parameters. DESIGN: Retrospective cohort study. SETTING: Fertility clinic. PATIENT(S): We analyzed data from 610 women who underwent homologous or donor double IUI from 2005 to 2010 and whose data of uterine contractions or follicle rupture were recorded. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live-birth rate. RESULT(S): Nine hundred seventy-nine IUI cycles were included. The detection of follicle rupture (odds ratio [OR], 1.98; 95% confidence interval [CI], 1.30-3.01) and the number of uterine contractions per minute (OR, 1.67; 95% CI, 1.02-2.74) assessed after the second insemination procedure of a double IUI were positively correlated with the live-birth rate. A multiple logistic regression model showed that sperm origin, maternal age, follicle count at hCG administration day, follicle rupture, and the number of uterine contractions observed after the second insemination procedure were significantly associated with the live-birth rate. CONCLUSION(S): Follicle rupture and uterine contractions are associated with the success of an IUI cycle. This may open new possibilities to improve the methodology of IUI.

Heterotopic pregnancy following intrauterine insemination: successful management with salpingectomy and continuation of intrauterine pregnancy.

We report the first case of a heterotopic pregnancy (HP) following ovulation induction and intrauterine insemination (IUI) with resultant normal intrauterine pregnancy after salpingectomy. A 41-year-old para 0 +0 that presented with primary infertility due to azoospermia and polycystic ovaries after laparoscopic evaluation. She had induction of ovulation with Clomiphene citrate, gonadotropin stimulation (hCG), and intrauterine insemination using donor sperm. The resulting pregnancy was later diagnosed as heterotopic pregnancy following rupture of the tubal component at 8 weeks' gestation after an initial misdiagnosis as corpus luteum cyst of pregnancy. She had an emergency laparotomy and left salpingectomy, and the intrauterine pregnancy has continued subsequently to 25 weeks of gestation as at 01/04/2011.This report demonstrates that HP may occur after ovulation induction and IUI. The ectopic component could be misdiagnosed as corpus luteum cyst. It is recommended that pregnancies following this procedure be followed up with serial trans-vaginal ultrasound in the first trimester. Presence of corpus luteum cyst of pregnancy in early ultrasound should be an index of suspicious of a possible heterotopic pregnancy. Early diagnosis and prompt intervention is essential to salvage the intrauterine pregnancy and avoid maternal morbidity and mortality.

Report of results obtained in 2,934 women using donor sperm: donor insemination versus in vitro fertilization according to indication.

OBJECTIVE: To demonstrate that the use of donor sperm leads to varying outcome rates and that its use has evolved. DESIGN: Retrospective observational cohort study. SETTING: University-affiliated private IVF setting. PATIENT(S): Women (2,934) undergoing donor insemination (DI) or IVF with donor sperm (IVF-D). INTERVENTION(S): None. MAIN OUTCOME MEASUREMENT(S): We evaluated the distribution of the clinical indications for the use of donated sperm, studying the reproductive outcome. RESULT(S): A total of 1,663 DI (57%) and 1,271 IVF-D (43%) were performed. There were significant differences in the indications for the use of donated sperm (DI vs. IVF-D). Regarding pregnancy rates (PR), cases of nonobstructive azoospermia presented the highest rate (29.1%), whereas cases of intracytoplasmic sperm injection (ICSI) failures and single women showed rates of 27.6% and 22.6%, respectively. Meanwhile, patients with ICSI failures achieved the highest PRs in IVF cycles (48.7%), whereas nonobstructive azoospermia and single women showed rates of 42.0% and 38.2%, respectively. There have been significant increases in the use of donated sperm in single women. CONCLUSION(S): Single women, which also represented the oldest group, show a lower probability of achieving pregnancy, and thus represent a subfertile population. Associated factors could include advanced maternal age.

Avoiding legal pitfalls in surrogacy arrangements.

The goal of this article is to discuss the legal pitfalls that reproductive endocrinologists face when participating in gestational surrogacy contracts. This paper was composed using Westlaw and LexisNexis commercial legal search engines to perform a review of statutes and cases pertaining to gestational surrogacy. The search results demonstrated that in the absence of suitable preparation, there is significant potential for litigation while participating in gestational agreements. Providers caring for gestational carriers have been named as parties in lawsuits for failure to provide psychological screening, failure to screen for infectious disease and participation in gestational contracts that are not compliant with state law. There is great disparity in state laws and court rulings pertaining to gestational agreements. When legal disputes arise, individual state laws and court rulings are controlling over the Uniform Parentage Act. Likewise, recommendations by the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine do not supersede state laws. The failure to abide by individual state laws unnecessarily exposes reproductive endocrinologists and their IVF facilities to potential litigation. In order to lessen exposure to litigation, an understanding of individual state legislation or historical court rulings is advised.

Is the use of donor sperm associated with a higher incidence of preeclampsia in women who achieve pregnancy after intrauterine insemination?

OBJECTIVE: To evaluate the incidence of preeclampsia after intrauterine insemination (IUI) with either donor's or partner's sperm in women with primary infertility. DESIGN: Retrospective cohort study. SETTING: Tertiary referral center. PATIENTS: Between January 1999 and December 2006, 823 women who achieved pregnancy after IUI and delivered at > or =24 weeks of gestation were reviewed. Only women with primary infertility and no known medical disorders were included. On the basis of the available outcome data, the final analysis was performed in 713 pregnancies (438 pregnancies using donor's sperm and 275 pregnancies using partner's sperm). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): The incidence of preeclampsia. RESULT(S): The incidence of preeclampsia in pregnancies resulting from donor sperm was higher than in the partner insemination group: 10.9% (48/438) versus 7.2% (20/275), respectively (difference, 3.7; 95% confidence interval -0.8 to +7.8). Logistic regression was performed controlling for the following parameters: type of sperm, number of previous cycles, and number of babies. In the final model, the variables that significantly predicted the risk of preeclampsia were the type of sperm used for insemination and the number of previous IUI cycles performed. The fewer cycles that were performed, the higher the incidence of preeclampsia that was observed. CONCLUSION(S): IUI with donor sperm appears to increase the incidence of preeclampsia when pregnancy is achieved. A protective effect of multiple cycles appears also to be present in this respect.

Is there a real risk of transmitting variant Creutzfeldt-Jakob disease by donor sperm insemination?

Although >99% of cases of Creutzfeldt-Jakob disease (CJD) are caused by spontaneous or inherited mutations in the prion protein, 'variant' CJD (vCJD) arose from dietary exposure to meat products infected with the bovine spongiform encephalopathy prion. While European and Canadian sperm donor candidates are rejected for significant CJD risk factors, American sperm donors are managed like blood donors (excluding all men who spent > or =3 months in the UK during 1980-1996 or > or =5 years in Europe since 1980), even though no evidence exists for sexual transmission of prion disease. This study surveyed international experts on either prions/prion disease or donor sperm/cryobanking as to the risk of vCJD transmission via semen/donor spermatozoa (45/104 replied). Consensus expert opinion was that the risk of transmission was <1:10,000,000, even for UK men, hence ultra-conservative risk avoidance would have minimal impact on public safety. Defining 'high vCJD risk' should be based on knowledge rather than fear, and due caution founded upon quantifying real risks rather than avoiding theoretical risks. Women seeking treatment using donor spermatozoa should be allowed to judge the negligible risk of vCJD infection in comparison with acceptable everyday risks, and given the choice of accepting spermatozoa from donors screened according to European-style criteria.