Reproductive effects of prolonged experimentally induced hypothyroidism in bitches.

BACKGROUND: Hypothyroidism has detrimental effects on reproduction in females of many species. Studies of hypothyroidism in bitches are limited and results conflicting. HYPOTHESIS: Hypothyroidism interferes with reproductive function and health of offspring in bitches. ANIMALS: A total of 9 healthy mixed-breed bitches (control) and 9 mixed breed bitches with hypothyroidism induced by radioactive iodine administration. METHODS: Dogs in both groups were bred 20.9 ± 4.0 and 56 ± 7.6 weeks after radioiodine administration in the hypothyroid group and again after levothyroxine was administered for 37 ± 14 weeks to hypothyroid dogs. Measures of the estrus cycle, fertility, gestation, whelping, and pup health were evaluated at each breeding. Comparisons were made between hypothyroid and control dogs as well as within groups between times. RESULTS: Pregnancy was documented in all dogs in both groups at the 1st breeding, 4/8 and 6/6 untreated hypothyroid and control dogs, respectively, at the 2nd breeding, and 6/6 and 5/6 treated hypothyroid and control dogs, respectively, at the 3rd breeding. Periparturient mortality was higher and birth weight was lower in pups born to untreated hypothyroid dogs compared with control dogs or treated hypothyroid dogs. There was no difference in interestrus interval, gestation duration, breeding behavior, interval between birth of pups, or serum progesterone concentrations at any breeding between or within groups. Resolution of hypothyroidism reversed the detrimental effects of thyroid hormone deficiency on reproduction. CONCLUSIONS AND CLINICAL IMPORTANCE: Hypothyroidism causes reversible periparturient mortality and low birth weight in offspring. Further investigation is necessary to determine if fertility is affected.

Do women with unexplained recurrent pregnancy loss have higher day 3 serum FSH and estradiol values?

OBJECTIVE: To determine the potential role of diminished ovarian reserve in unexplained habitual abortion. DESIGN: Retrospective comparative analysis. SETTING: University-based practice. PATIENT(S): Fifty-seven women who presented for evaluation of recurrent pregnancy loss (RPL). INTERVENTION(S): The test group (n = 36) comprised women with unexplained RPL. The control group (n = 21) comprised women with a known cause of RPL. Mean age, parity, day 3 serum FSH and E(2) levels, and presence or absence of a history of infertility were compared between groups. MAIN OUTCOME MEASURE(S): Day 3 serum FSH and E(2) levels. RESULT(S): Both day 3 FSH and E(2) levels were elevated in the unexplained group compared with the control group. When combined, FSH or E(2) levels, or both, were elevated in 58% of the unexplained RPL group and 19% of the control group (odds ratio, 5.95 [95% CI, 1.7-21.3]; P<.004). Age, parity, and presence of infertility did not differ between groups. CONCLUSION(S): Women with unexplained RPL have a greater incidence of elevated day 3 serum FSH and E(2) levels than do women with a known cause of RPL. Therefore, diminished ovarian reserve may contribute to recurrent pregnancy loss and should be considered part of the work-up for RPL.

Deglycosylation of a bifunctional lutropin-follitropin agonist reduced its follitropin activity more than its lutropin activity.

OBJECTIVE: To design a drug that blocks the gonadal actions of lutropins and follitropins. DESIGN: Controlled in vitro study. SETTING: Academic laboratory. PATIENT(S): None. INTERVENTION(S): We removed three glycosylation signals from an hCG-hFSH chimera known to have high affinity for LH and FSH receptors, expecting this would create a bifunctional antagonist (dgCFC). To offset the inhibition of subunit combination caused by deglycosylation of alpha-subunit loop 2, we prepared dgCFC as a single-chain fusion protein containing the alpha-subunit downstream of the chimeric beta-subunit. MAIN OUTCOME MEASURE(S): Receptor binding, cyclic adenosine monophosphate accumulation. RESULT(S): dgCFC bound LH or FSH receptors similar to hCG or hFSH. It was a partial agonist and had one tenth the efficacy of hFSH and two thirds the efficacy of hCG. CONCLUSION(S): The surprising high residual lutropin activity of dgCFC indicated that its FSH residues offset the effects of deglycosylation, suggesting this approach to preparing a bifunctional antagonist is unlikely to lead to a useful drug. The increased lutropin efficacy of dgCFC relative to deglycosylated hCG supports the idea that oligosaccharides modulate glycoprotein hormone efficacy through an influence on hormone conformation.

Fallopian sperm perfusion versus intrauterine insemination: a randomized controlled trial and metaanalysis of the literature.

OBJECTIVE: To determine whether fallopian sperm perfusion significantly improves pregnancy rates over intrauterine insemination (IUI) in infertile patients. DESIGN: Prospective, randomized, controlled trial and metaanalysis of the literature. SETTING: University-based infertility practice. PATIENT(S): Patients undergoing controlled ovarian stimulation were included in the prospective trial. They were <40 years of age and had no tubal obstructions, and their partners had no history of severe oligospermia. The metaanalysis was done using the patients with unexplained infertility from this study and from other randomized controlled trials found through a MEDLINE data base search. INTERVENTION(S): After undergoing controlled ovarian stimulation, the patients were randomly assigned to receive either IUI or fallopian sperm perfusion. MAIN OUTCOME MEASURE(S): Clinical pregnancy rates. RESULT(S): Only the patients with unexplained infertility had a statistically higher pregnancy rate with fallopian sperm perfusion (odds ratio, 4.1; confidence interval, 1.1-16.4). A metaanalysis of the prospective randomized trials that provided data on patients with unexplained infertility showed a significant improvement in pregnancy rates with fallopian sperm perfusion (odds ratio, 1.9; confidence interval, 1.2-3). CONCLUSION(S): Fallopian sperm perfusion does not improve the chances of pregnancy in patients with infertility other than those with unexplained infertility. Fallopian sperm perfusion does significantly improve the pregnancy rates of patients with unexplained infertility who undergo controlled ovarian stimulation with gonadotropin/insemination protocols.

Conscious sedation for in vitro fertilization.

OBJECTIVE: To review the principles and practice of the use of conscious sedation for IVF. DESIGN: The pertinent literature was reviewed and recommendations are provided. RESULT(S): Conscious sedation appears to be the most commonly used method of pain relief for transvaginal retrieval of oocytes. Conscious sedation does not require the presence of an anesthesiologist and can be done in freestanding clinics. Agents commonly used include opioids in combination with benzodiazepines. This combination minimizes pain, decreases anxiety, and provides sedation and some amnesia. Adjuvants such as promethazine and hydroxyzine can also be used but often are not needed. Conscious sedation is well tolerated by patients and does not require highly specialized equipment. However, there are specific safeguards that should be followed. Only a few toxicity studies have been performed, but they are reassuring because they have not found significant effects on fertilization or cleavage. CONCLUSION(S): Conscious sedation appears to be a safe and cost-effective method of providing analgesia and anesthesia for transvaginal retrieval of oocytes.

Vulvar edema as a complication of laparoscopic surgery.

Vulvar edema occurred in three women within 24 hours after operative laparoscopy. In addition to local swelling and discomfort, inability to void was a common complaint. All three patients were treated with Foley catheter urinary drainage, local application of ice packs, and bedrest for 1 to 2 days with spontaneous resolution of the edema. We conclude that vulvar edema is a possible complication of endoscopy. Although it may require hospitalization because of inability to void, the condition is self-limited.