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undergoing IVF due to studies demonstrating higher SET and live birth rates after aneuploidy testing. In contrast, recent RCTs have failed to reproduce these results, raising important questions about patient selection, publication bias and testing platforms in the initial studies.
Safety ofART
Transfer of multiple embryos and multiple pregnancies contributed to the initial adverse obstetric and perinatal outcomes associated with ART. However, the increasing utilization of SET has resulted in lower multiple pregnancy rates, thereby decreasing obstetric and perinatal risks. Yet, the safety of ART, speci cally ICSI, has been questioned given that the fertilizing spermatozoon is selected arbitrarily, and it neither binds to the zona pellucida nor fuses with oolemma. Thus far, studies of ICSI children have provided suf cient information to reassure these qualms. Population based studies have suggested a modest increase in small for gestational age babies (SGA), low birthweight (LBW), and preterm birth (PTB) with fresh embryo transfer and large-for-gestational age (LGA) babies and pre-eclampsia with FET.
Discussion
The patient in the current clinical case has poor ovarian reserve as exempli ed by her ovarian reserve markers. Women with low ovarian reserve constitute a large number of IVF cases in the U.S.; however, treatment of women with poor ovarian reserve may not be straightforward. Women with high cycle day 2/3 FSH or low AMH often do not respond well to ovarian stimulation and/or may be at high risk of IVF cycle cancelation prior to oocyte retrieval. Furthermore, oocyte yield can be low even if oocyte retrieval is accomplished in such patients. Therefore, many clinics may not even consider ovarian stimulation for IVF in women with poor ovarian reserve and may encourage them to pursue treatment using donor oocytes.
The above patient presented to us with a history of elevated FSH and exceedingly low AMH levels. Due to poor ovarian reserve, she underwent three IVF cycles in another institution, together yielding a single cryopreserved 2 PN zygote. Given her high basal FSH level (>40 mIU/mL) and an LH level of 18 mIU/mL, she underwent a single gonadotropin stimulated cycle after luteal estradiol suppression which was canceled due to poor response. As both ovaries appeared to be devoid of any follicles, she was placed on transdermal estradiol 0.1 mg every 3 days with weekly ultrasound examinations. Her FSH subsequently decreased from 48.5 mIU/mL to 28.7 mIU/mL after 14 days of estradiol treatment. At this point, two tiny follicles were detected on ultrasound and GnRH-ant treatment in the form of daily subcutaneous Ganirelix acetate injection was initiated. This combination of transdermal
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estradiol and subcutaneous GnRH-ant resulted in further reduction of FSH levels to 7 mIU/mL. Menses was induced with a 10-day course of oral medroxyprogesterone acetate 10 mg. Baseline hormonal parameters on cycle day 2 of menses were as follows: E2 104 pg/mL; FSH 5.11 mIU/mL; LH 2.76 mIU/mL. Transdermal estradiol was discontinued, and ovarian stimulation was initiated with 150 units of recombinant FSH, 150 units of human menopausal gonadotropin (hMG) and daily Ganirelix acetate. Following 14 days of ovarian stimulation, two dominant follicles developed in the right ovary, and 10,000 IU of human chorionic gonadotropin (hCG) was administered as the ovulatory trigger. Two oocytes were retrieved 36 h later, both of which were mature and fertilized successfully with ICSI. A single day-3 13-cell embryo was transferred, which resulted in a clinical pregnancy. A single dayve, 3 BB blastocyst was also cryopreserved. The patient’s non-invasive prenatal screening at 10-week gestation returned normal, and she currently reports an ongoing clinical pregnancy at 16 weeks. The current case highlights that ovarian reserve parameters in isolation may not predict the probability of achieving a pregnancy with IVF, especially in young women with poor ovarian reserve. Critically, when basal LH levels are elevated, it is important to suppress LH levels as soon as stimulation is begun in order to prevent premature luteinization of growing follicles.
Conclusion
Infertility is a common clinical condition, and ART, speci cally IVF, remains its quintessential treatment strategy. Ef cient ovarian stimulation protocols, standardization oocyte retrieval technique, and successful laboratory techniques have contributed to improved live birth rates and lower complications. Increasing rates of SET cycles have further mitigated perinatal outcomes such as PTB, LBW, and perinatal mortality. Clinical data regarding the long-term health of ART-conceived children remain reassuring.
Suggested Readings
1.\ Huang JY, Rosenwaks Z. Assisted reproductive techniques. Methods Mol Biol. 2014;1154:171–231.
2.\ Palermo GD, Kocent J, Monahan D, Neri QV, Rosenwaks Z. Treatment of male infertility. Methods Mol Biol. 2014;1154:385–405.
3.\ Pereira N, Petrini AC, Hancock KL, Rosenwaks Z. Fresh or frozen embryo transfer in in vitro fertilization: an update. Clin Obstet Gynecol. 2019;62(2):293–9.
4.\ Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, Warner L, Kroelinger CD, Bar eld WD. Assisted Reproductive Technology Surveillance-United States, 2018. MMWR Surveill Summ. 2022;71(4):1–19.
5.\ Palermo GD, Neri QV, Schlegel PN, Rosenwaks Z. Intracytoplasmic sperm injection (ICSI) in extreme cases of male infertility. PLoS One. 2014;9(12):e113671.
Chapter 31
Ovarian Hyperstimulation Syndrome (OHSS)
Alexis Melnick and Zev Rosenwaks
Case Part 1
A 33-year-old G0 with a history of polycystic ovary syndrome presents to the emergency room 2 weeks after an intrauterine insemination (IUI) performed by an outside reproductive endocrinologist. We were consulted on her complaint of increasing abdominal distention and discomfort. She reports feeling well until 2 days post-IUI when she began to notice increased abdominal distension and intermittent, sharp pain particularly with ambulation and movement. For the past 2 days, she reports nausea and vomiting and has not been able to keep down both solids and liquids for the past day. She denies fevers, chills, chest pain, shortness of breath or dizziness. She notices that she has been urinating less than usual and reports a weight gain of 8 pounds since the start of her IUI cycle. She provides a summary of her recent treatment from her doctor:
––IUI cycle #1: Clomiphene citrate 50 mg/day (day 3–7), max E2 400 pg/mL, developed 1–2 follicles, neg pregnancy test.
––IUI cycle #2 (current cycle which brought her to the ER):
FSH 150 iu + hMG 75 iu starting dose on cycle day 2. Decreased to 75 iu +75 iu starting cycle day 7 till day of trigger,
A. Melnick · Z. Rosenwaks (*)
Reproductive Medicine and Ob/Gyn, The Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine, Weill Medical College of Cornell University, New York, NY, USA e-mail: alm2036@med.cornell.edu; zrosenw@med.cornell.edu
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5 follicles >/=15 mm on day of trigger (10,000 iu hCG) E2 1998 pg/mL at trigger.
E2 3116 pg/mL on day of IUI.
Her gynecologic history is signi cant for PCOS diagnosed in her late teens. She typically has 6–8 menstrual periods per year and is unable to track her ovulation with ovulation predictor kits. Both she and her partner had otherwise normal workups with her fertility doctor. Her past medical and surgical history are unremarkable other than an uncomplicated laparoscopic appendectomy at age 14. She takes a daily prenatal vitamin and acetaminophen as needed for occasional headaches.
Evaluation
Evaluation of this patient should include:
•\ Detailed history of fertility treatment including type and doses of medication, peak estradiol levels, number of follicles at ovulatory trigger, number of eggs retrieved/embryos transferred (if IVF).
•\ Complete physical exam including:
––Vitals signs.
––Weight.
––Abdominal circumference.
––Abdominal exam.
––Lower extremity exam.
•\ Laboratory evaluation including:
––Serum hCG.
––Estradiol (E2), Progesterone (P4).
––CBC.
––Basic metabolic pro le.
––Hepatic function pro le. •\ Imaging:
––Pelvic sonogram.
––Chest X-ray (if there is concern for pleural effusion or pulmonary edema).
––Dopplers (if there is concern for venous thromboembolism).
Differential Diagnosis
•\ Ovarian hyperstimulation syndrome. •\ Ruptured ovarian cyst.