Jarl A. Kahn

Exposure to high levels of luteinizing hormone and estradiol in the early follicular phase of gonadotropin-releasing hormone antagonist cycles is associated with a reduced chance of pregnancy

OBJECTIVE To compare ongoing implantation rates under two different GnRH antagonist protocols. DESIGN Randomized controlled trial. SETTING Tertiary referral center. PATIENT(S) One hundred eleven women undergoing ovarian stimulation for in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S) Ovarian stimulation with 150 IU recombinant-FSH (rec-FSH) starting on day 2 of the cycle and GnRH antagonist starting either on day 6 of stimulation (fixed group) or when a follicle of > or = 15 mm was present after at least 5 days of stimulation (flexible group). In the flexible group, the rec-FSH dose was increased to 250 IU when the antagonist was initiated. MAIN OUTCOME MEASURE(S) Ongoing implantation and pregnancy rate. RESULT(S) In patients with no follicle of > or = 15 mm present on day 6 of stimulation, a significantly lower ongoing implantation rate was observed if the flexible scheme was applied as compared with the fixed scheme of administration (8.8% vs. 23.9%, respectively). Exposure of the genital tract to LH or E2 from initiation of stimulation to antagonist administration was able to distinguish between pregnant and nonpregnant patients in the population studied. CONCLUSION(S) High exposure of the genital tract to LH and E2 in the early follicular phase is associated with a reduced chance of pregnancy in cycles stimulated with recombinant FSH and GnRH antagonist for IVF/ICSI.

Gestational age in pregnancies conceived after in vitro fertilization: a comparison between age assessed from oocyte retrieval, crown‐rump length and biparietal diameter

Objective  To compare gestational age (GA) and day of delivery estimated from the time of in vitro fertilization (IVF) (oocyte retrieval + 14 days), the ultrasonic measurement of the crown–rump length (CRL) and the biparietal diameter (BPD) in pregnancies conceived in an IVF setting.

DNA strand breaks in human sperm cells, A comparison between men with normal and oligozoospermic sperm samples

BACKGROUND The aim of this report was to compare the degree of DNA strand breaks in known normal fertile men to those with oligozoospermia, and evaluate the presence of DNA strand breaks in normal raw sperm, after Percoll and swim-up and following conventional cryopreservation, as all these preparation methods might differ in selection of healthy sperm cells. METHODS Sperm samples from proven fertile sperm donors (n=20) and infertile men with oligozoospermia (n=33) were tested for the presence of DNA strand breaks in the spermatozoa, by direct immunoperoxidase detection of digoxigenin-labeled genomic DNA. A correlation to other sperm parameters, sperm counts, motility and Krügers strict criteria was performed. RESULTS DNA strand breaks were found significantly more often in sperm samples from men with oligozoospermia compared to sperm samples of normal fertile men. The degree of spermatozoa with DNA strand breaks was correlated proportional with the degree of morphological pathological sperm cells judged by Krügers strict criteria. The percentage of spermatozoa with DNA strand breaks in the samples was not influenced by procedures such as the swim-up technique, Percoll gradients or cryopreservation and thawing. CONCLUSION DNA strand breaks were found significantly more often in men with oligozoospermia compared to normospermic men. The DNA strand breaks might play an important role for the maturation process of the spermatozoa in the same way as apoptosis is controlling the number of early meiotic germ cells in the testis, and hereby play an important role in advanced fertility treatments (ICSI).

Treatment of unexplained infertility: Fallopian tube sperm perfusion (FSP)

Patients and methods. Fifty‐one couples with unexplained infertility were enrolled in the fallopian tube sperm perfusion (FSP) program. FSP is in short a combination of ovarian hyperstimulation, ovulation induction and intrauterine and intrafallopian tube insemination using a sperm suspension of 4 ml volume.

Placenta accreta and methotrexate treatment

extracts (1). In the United States, these products are used by millions of people to promote weight loss and/ or enhance athletic performance everyday. However, ephedrine-containing athletic performance-enhancing products have been associated with serious adverse effects, including myocardial infarction, cardiac arrhythmias, hypertension, seizures, stroke, and death (2,3). Most of these complications have been reported in young healthy adults (in an absence of any pre-existing disease) and have not appeared to be dose related (4). Foxford et al. (3) recently described the occurrence of a severe vasospasm-induced headache, which progressed to vasospasm-induced stroke in a previously healthy varsity athlete secondary to ephedrine ingestion. The authors concluded that every effort should be made to educate the athletes about hidden ingredients (such as ephedrine) in performance-enhancing products and the serious health risks associated with their use for athletic performance (3). Ephedrine is a sympathomimetic agent similar in molecular structure to amphetamines (5). Pregnancy enhances the cardiovascular and central nervous system toxicity of sympathomimetic drugs such as cocaine, amphetamines, and ephedrine (6). It has been reported that even small recreational sympathomimetic drug ingestion may cause vasoconstriction of the epicardial coronary arteries and/or intracranial vessels. In this report, the severe ephedrine ingestionrelated (vasospasm-induced) headache in an otherwise healthy pregnant athlete luckily did not result in any morbidity; however, it created a diagnostic dilemma and was at presentation mistaken for a common pregnancy-specific disorder (pregnancy-inducted hypertension). The differential diagnosis also included intracranial pathology (e.g. stroke or rupture of an aneurysm). This case report clearly demonstrates that the diverse (and often unpredictable) clinical manifestations of acute ephedrine-containing nutritional supplements intake, when combined with physiologic changes of pregnancy, and pathophysiology of co-existing pregnancy-specific disease (if present) might result in significant complications and impact the maternal and fetal well-being. In conclusion, the purpose of this case report is to alert the pregnant athlete women of the hidden risks associated with nutritional supplements use/misuse in pregnancy.

GnRH antagonists in poor responders

Gonadotropin releasing hormone (GnRH) antagonists allow endogenous gonadotropins to enhance stimulation in the first part of the follicular phase until there is a need to inhibit the premature luteinizing hormone (LH) surge and this might represent a stimulation option for poor responders (1–3). We hypothesized that an increase in the dose of gonadotropins in combination with the use of GnRH antagonists would improve the stimulation and pregnancy outcome in poor responders previously treated unsuccessfully with GnRH agonists for intracytoplasmic sperm injection (ICSI).

Hyperreactio luteinalis, presented as an acute abdomen

We describe a rare case of an Arias-Stella reaction in an adenomyomatous polyp of the endometrium found in the first trimester of pregnancy. A 33-year-old Japanese woman, gravida 1, para 1, presented for an initial prenatal examination at 6-week gestation; ultrasound revealed a myoma-like solid mass in the cervical canal. An abnormal Papanicolaou’s smear (highly suspicious of adenocarcinoma) prompted the resection of this pedunculated polyp. Histologically, the musculature located in the center of the polyp was covered by the endometrium; numerous glands within both the endometrium and the musculature exhibited an Arias-Stella reaction. This explains the result of Papanicolaou’s smear, because subsequent smears * both intrapartum and postpartum * were negative. To our knowledge, this is the first reported incident of an Arias-Stella reaction in an adenomyomatous polyp. This could be one of the diagnostic pitfalls in Papanicolaou’s smears taken during pregnancy.

Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter ‘extended pilot study’

To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when ≤ 5 follicles developed in a preceding cycle following a long agonist protocol with the use of > 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5 before expected start of menstruation and continued for 4–7 days. On cycle day 2–3 a starting dose of rFSH (300–400 IU/day) was given. At a leading follicle diameter of 14 mm, ganirelix administration was resumed until final oocyte maturation was induced with 10,000 IU hCG. GnRH antagonist only marginally affected the intercycle FSH rise; basal levels of FSH remained similar to those seen after 4 days of antagonist administration. The protocol effectively induced low LH levels and luteolysis, but daily administration of 350 IU rFSH (median) for 11 days only led to the collection of 3 oocytes in 49 oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release may improve the stimulation results in poor responders.

A Spleen Pregnancy

Non‐tubal ectopic pregnancy is very rare. We report a case of spleen pregnancy, difficult to recognize clinically. The tests and investigations which led to the diagnosis and treatment are described briefly.

Insulin producing primary ovarian carcinoid tumor

Carcinoid tumors are slow growing and originate most frequently from gastrointestinal tissue (1) . They may also appear in genital tissue like the ovaries. Primary ovarian carcinoid tumors are rare and contribute to less than 0.1% of all ovarian carcinomas (2) .